Kras

Summary

Gene Symbol: Kras
Description: Kirsten rat sarcoma viral oncogene homolog
Alias: AI929937, K-Ras, K-Ras 2, K-ras, Ki-ras, Kras-2, Kras2, c-K-ras, c-Ki-ras, p21B, ras, GTPase KRas, Kirsten rat sarcoma oncogene 2, expressed, p21 protein, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
Species: mouse
Products:     Kras

Top Publications

  1. Morton J, Timpson P, Karim S, Ridgway R, Athineos D, Doyle B, et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci U S A. 2010;107:246-51 pubmed publisher
    ..in 50-75% of human pancreatic ductal adenocarcinomas (PDAC) following an initiating activating mutation in the KRAS gene...
  2. Neesse A, Frese K, Bapiro T, Nakagawa T, Sternlicht M, Seeley T, et al. CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer. Proc Natl Acad Sci U S A. 2013;110:12325-30 pubmed publisher
    ..Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models, and by extension in PDA patients. ..
  3. Viale A, Pettazzoni P, Lyssiotis C, Ying H, Sánchez N, Marchesini M, et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014;514:628-32 pubmed publisher
    ..b>KRAS mutations are known to be a driver event of PDAC, but targeting mutant KRAS has proved challenging...
  4. Courtin A, Richards F, Bapiro T, Bramhall J, Neesse A, Cook N, et al. Anti-tumour efficacy of capecitabine in a genetically engineered mouse model of pancreatic cancer. PLoS ONE. 2013;8:e67330 pubmed publisher
    ..Using a model of spontaneous PDAC occurring in Kras(G12D); p53(R172H); Pdx1-Cre (KPC) mice and subcutaneous allografts of a KPC PDAC-derived cell line (K8484), we ..
  5. Aytes A, Mitrofanova A, Kinkade C, Lefebvre C, Lei M, Phelan V, et al. ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer. Proc Natl Acad Sci U S A. 2013;110:E3506-15 pubmed publisher
    ..Using an inducible Cre driver to simultaneously inactivate Pten while activating oncogenic Kras and a fluorescent reporter allele in the prostate epithelium, we performed lineage tracing in vivo to define the ..
  6. Yang X, La Rosa F, Genova E, Huber K, Schaack J, DeGregori J, et al. Simultaneous activation of Kras and inactivation of p53 induces soft tissue sarcoma and bladder urothelial hyperplasia. PLoS ONE. 2013;8:e74809 pubmed publisher
    ..Our original intention of this study was to investigate the role of Kras and p53 in the development of urinary bladder cancer...
  7. Feig C, Jones J, Kraman M, Wells R, Deonarine A, Chan D, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A. 2013;110:20212-7 pubmed publisher
    ..The residual tumor was composed only of premalignant epithelial cells and inflammatory cells. Thus, a single protein, CXCL12, from a single stromal cell type, the FAP(+) CAF, may direct tumor immune evasion in a model of human PDA. ..
  8. Rosenfeldt M, O Prey J, Morton J, Nixon C, Mackay G, Mrowinska A, et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature. 2013;504:296-300 pubmed publisher
    ..Mice with pancreases containing an activated oncogenic allele of Kras (also called Ki-Ras)--the most common mutational event in PDAC--develop a small number of pre-cancerous lesions ..
  9. Saborowski M, Saborowski A, Morris J, Bosbach B, Dow L, Pelletier J, et al. A modular and flexible ESC-based mouse model of pancreatic cancer. Genes Dev. 2014;28:85-97 pubmed publisher
    ..The ESCs harbor a latent Kras mutant (a nearly ubiquitous feature of pancreatic cancer), a homing cassette, and other genetic elements needed for ..

More Information

Publications100

  1. Morris J, Greer R, Russ H, von Figura G, Kim G, Busch A, et al. Dicer regulates differentiation and viability during mouse pancreatic cancer initiation. PLoS ONE. 2014;9:e95486 pubmed publisher
    ..in PDA development by deleting the miRNA processing enzyme Dicer in a PDA mouse model driven by oncogenic Kras. We find that loss of Dicer accelerates Kras driven acinar dedifferentiation and acinar to ductal metaplasia (ADM), ..
  2. Rhim A, Oberstein P, Thomas D, Mirek E, Palermo C, Sastra S, et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014;25:735-47 pubmed publisher
    ..Together, these data demonstrate that some components of the tumor stroma can act to restrain tumor growth. ..
  3. Ozdemir B, Pentcheva Hoang T, Carstens J, Zheng X, Wu C, Simpson T, et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014;25:719-34 pubmed publisher
    ..This study underscores the need for caution in targeting carcinoma-associated fibroblasts in PDAC. ..
  4. Lee J, Perera R, Wang H, Wu D, Liu X, Han S, et al. Stromal response to Hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci U S A. 2014;111:E3091-100 pubmed publisher
    ..mouse models and found that Hh pathway inhibition accelerates rather than delays progression of oncogenic Kras-driven disease...
  5. von Figura G, Fukuda A, Roy N, Liku M, Morris Iv J, Kim G, et al. The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma. Nat Cell Biol. 2014;16:255-67 pubmed publisher
    ..we find that loss of Brg1, a core subunit of SWI/SNF chromatin remodelling complexes, cooperates with oncogenic Kras to form cystic neoplastic lesions that resemble human IPMN and progress to PDA...
  6. Desai T, Brownfield D, Krasnow M. Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature. 2014;507:190-4 pubmed publisher
    ..AT2 self-renewal is selectively induced by EGFR (epidermal growth factor receptor) ligands in vitro and oncogenic Kras(G12D) in vivo, efficiently generating multifocal, clonal adenomas...
  7. Aguilera K, Rivera L, Hur H, Carbon J, Toombs J, Goldstein C, et al. Collagen signaling enhances tumor progression after anti-VEGF therapy in a murine model of pancreatic ductal adenocarcinoma. Cancer Res. 2014;74:1032-44 pubmed publisher
    ..Together, these findings suggest that collagen actively promotes PDA spread and that enhanced disease progression associated with anti-VEGF therapy can arise from elevated extracellular matrix-mediated signaling. ..
  8. Kapoor A, Yao W, Ying H, Hua S, Liewen A, Wang Q, et al. Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer. Cell. 2014;158:185-197 pubmed publisher
    Activating mutations in KRAS are among the most frequent events in diverse human carcinomas and are particularly prominent in human pancreatic ductal adenocarcinoma (PDAC)...
  9. DelGiorno K, Hall J, Takeuchi K, Pan F, Halbrook C, Washington M, et al. Identification and manipulation of biliary metaplasia in pancreatic tumors. Gastroenterology. 2014;146:233-44.e5 pubmed publisher
    ..We analyzed pancreatic tissue and tumors that developed in mice that express an activated form of Kras (Kras(LSL-G12D/+);Ptf1a(Cre/+) mice)...
  10. Wislez M, Spencer M, Izzo J, Juroske D, Balhara K, Cody D, et al. Inhibition of mammalian target of rapamycin reverses alveolar epithelial neoplasia induced by oncogenic K-ras. Cancer Res. 2005;65:3226-35 pubmed
    ..Here, we report that mTOR inhibition blocked malignant progression in K-ras(LA1) mice, which undergo somatic activation of the K-ras oncogene and display morphologic changes in alveolar ..
  11. Liu W, Monahan K, Pfefferle A, Shimamura T, Sorrentino J, Chan K, et al. LKB1/STK11 inactivation leads to expansion of a prometastatic tumor subpopulation in melanoma. Cancer Cell. 2012;21:751-64 pubmed publisher
    ..By somatically inactivating Lkb1 with K-Ras activation (±p53 loss) in murine melanocytes, we observed variably pigmented and highly metastatic melanoma with ..
  12. Provenzano P, Cuevas C, Chang A, Goel V, Von Hoff D, Hingorani S. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell. 2012;21:418-29 pubmed publisher
    ..In combination with the standard chemotherapeutic, gemcitabine, the treatment permanently remodels the tumor microenvironment and consistently achieves objective tumor responses, resulting in a near doubling of overall survival...
  13. Walter G, Ruediger R. Mouse model for probing tumor suppressor activity of protein phosphatase 2A in diverse signaling pathways. Cell Cycle. 2012;11:451-9 pubmed publisher
    ..Here, we report that PP2A functions as a tumor suppressor in mice that develop lung cancer triggered by oncogenic K-ras. We discuss whether PP2A may function as a tumor suppressor in diverse tissues, with emphasis on endometrial and ..
  14. Liao J, Wolfman J, Wolfman A. K-ras regulates the steady-state expression of matrix metalloproteinase 2 in fibroblasts. J Biol Chem. 2003;278:31871-8 pubmed
    ..Expression of a dominant-negative Ras protein significantly inhibited MMP-2 transcription, thereby suggesting a role for steady-state Ras function in the ..
  15. Grippo P, Nowlin P, Demeure M, Longnecker D, Sandgren E. Preinvasive pancreatic neoplasia of ductal phenotype induced by acinar cell targeting of mutant Kras in transgenic mice. Cancer Res. 2003;63:2016-9 pubmed
    Activating mutation of the Kras oncogene is the most frequent and perhaps the earliest genetic alteration associated with pancreatic cancer...
  16. Plowman S, Williamson D, O Sullivan M, Doig J, Ritchie A, Harrison D, et al. While K-ras is essential for mouse development, expression of the K-ras 4A splice variant is dispensable. Mol Cell Biol. 2003;23:9245-50 pubmed
    In mammals, the three classical ras genes encode four highly homologous proteins, N-Ras, H-Ras, and the isoforms K-Ras 4A and 4B...
  17. Eser S, Reiff N, Messer M, Seidler B, Gottschalk K, Dobler M, et al. Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer. Cancer Cell. 2013;23:406-20 pubmed publisher
    Oncogenic Kras activates a plethora of signaling pathways, but our understanding of critical Ras effectors is still very limited...
  18. Mukherjee P, Basu G, Tinder T, Subramani D, Bradley J, Arefayene M, et al. Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition. J Immunol. 2009;182:216-24 pubmed
    ..The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRAS(G12D) mutation and that expresses human MUC1 as a self molecule...
  19. Cook N, Frese K, Bapiro T, Jacobetz M, Gopinathan A, Miller J, et al. Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma. J Exp Med. 2012;209:437-44 pubmed publisher
  20. Bayne L, Beatty G, Jhala N, CLARK C, Rhim A, Stanger B, et al. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell. 2012;21:822-35 pubmed publisher
    ..In humans, PDA tumor cells prominently expressed GM-CSF in vivo. Thus, tumor-derived GM-CSF is an important regulator of inflammation and immune suppression within the tumor microenvironment. ..
  21. Hung K, Maricevich M, Richard L, Chen W, Richardson M, Kunin A, et al. Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment. Proc Natl Acad Sci U S A. 2010;107:1565-70 pubmed publisher
    ..are either solely mutant in the Apc gene or in combination with another colon cancer-associated mutant gene, the Kras G12D allele...
  22. Bai H, Li H, Zhang W, Matkowskyj K, Liao J, Srivastava S, et al. Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia (PanIN) by capsaicin in LSL-KrasG12D/Pdx1-Cre mice. Carcinogenesis. 2011;32:1689-96 pubmed publisher
    ..the effect of capsaicin on pancreatitis and pancreatic intraepithelial neoplasia (PanIN) was determined in a mutant Kras-driven and caerulein-induced pancreatitis-associated carcinogenesis in LSL-Kras(G12D)/Pdx1-Cre mice...
  23. Ying H, Kimmelman A, Lyssiotis C, Hua S, Chu G, Fletcher Sananikone E, et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 2012;149:656-70 pubmed publisher
    ..Oncogenic Kras mutation is the signature event in pancreatic ductal adenocarcinoma (PDAC), serving a critical role in tumor ..
  24. Olive K, Jacobetz M, Davidson C, Gopinathan A, McIntyre D, Honess D, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009;324:1457-61 pubmed publisher
    ..Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer...
  25. Tuveson D, Shaw A, Willis N, Silver D, Jackson E, Chang S, et al. Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects. Cancer Cell. 2004;5:375-87 pubmed
    Activating mutations in the ras oncogene are not considered sufficient to induce abnormal cellular proliferation in the absence of cooperating oncogenes...
  26. Singh A, Greninger P, Rhodes D, Koopman L, Violette S, Bardeesy N, et al. A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival. Cancer Cell. 2009;15:489-500 pubmed publisher
    K-ras mutations occur frequently in epithelial cancers...
  27. Hingorani S, Petricoin E, Maitra A, Rajapakse V, King C, Jacobetz M, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 2003;4:437-50 pubmed
    To evaluate the role of oncogenic RAS mutations in pancreatic tumorigenesis, we directed endogenous expression of KRAS(G12D) to progenitor cells of the mouse pancreas...
  28. CARRIERE C, Gore A, Norris A, Gunn J, Young A, Longnecker D, et al. Deletion of Rb accelerates pancreatic carcinogenesis by oncogenic Kras and impairs senescence in premalignant lesions. Gastroenterology. 2011;141:1091-101 pubmed publisher
    ..Pancreatic ductal adenocarcinomas (PDACs) have a high frequency of mutations in KRAS and INK4A/CDKN2A that might allow cells to bypass the regulatory actions of retinoblastoma (RB)...
  29. Hollander M, Maier C, Hobbs E, Ashmore A, Linnoila R, Dennis P. Akt1 deletion prevents lung tumorigenesis by mutant K-ras. Oncogene. 2011;30:1812-21 pubmed publisher
    K-ras mutations are associated with smoking-induced lung cancer and poor clinical outcomes...
  30. Hill R, Calvopina J, Kim C, Wang Y, Dawson D, Donahue T, et al. PTEN loss accelerates KrasG12D-induced pancreatic cancer development. Cancer Res. 2010;70:7114-24 pubmed publisher
    b>KRAS mutations are found in ?90% of human pancreatic ductal adenocarcinomas (PDAC)...
  31. Hatley M, Patrick D, Garcia M, Richardson J, Bassel Duby R, van Rooij E, et al. Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. Cancer Cell. 2010;18:282-93 pubmed publisher
    ..MiR-21 drives tumorigenesis through inhibition of negative regulators of the Ras/MEK/ERK pathway and inhibition of apoptosis.
  32. Mito J, Min H, Ma Y, Carter J, Brigman B, Dodd L, et al. Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma. J Pathol. 2013;229:132-40 pubmed publisher
    ..mutations in miRNA biogenesis in sarcoma, we used primary soft tissue sarcomas expressing either Braf(V600E) or Kras(G12D)...
  33. Chen Z, Cheng K, Walton Z, Wang Y, Ebi H, Shimamura T, et al. A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response. Nature. 2012;483:613-7 pubmed publisher
    ..mouse models to conduct a 'co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers...
  34. Miyabayashi K, Ijichi H, Mohri D, Tada M, Yamamoto K, Asaoka Y, et al. Erlotinib prolongs survival in pancreatic cancer by blocking gemcitabine-induced MAPK signals. Cancer Res. 2013;73:2221-34 pubmed publisher
    ..is superior to gemcitabine alone in blocking progression and prolonging survival in a murine model of PDAC (Kras activation with Tgfbr2 knockout)...
  35. Premsrirut P, Dow L, Kim S, Camiolo M, Malone C, Miething C, et al. A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell. 2011;145:145-58 pubmed publisher
    ..This system provides a cost-effective and scalable platform for the production of RNAi transgenic mice targeting any mammalian gene. PAPERCLIP: ..
  36. Lee K, Bar Sagi D. Oncogenic KRas suppresses inflammation-associated senescence of pancreatic ductal cells. Cancer Cell. 2010;18:448-58 pubmed publisher
    Mutational activation of KRas is the first and most frequently detected genetic lesion in pancreatic ductal adenocarcinoma (PDAC). However, the precise role of oncogenic KRas in the pathogenesis of PDAC is not fully understood...
  37. Takahashi H, Ogata H, Nishigaki R, Broide D, Karin M. Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation. Cancer Cell. 2010;17:89-97 pubmed publisher
    ..initiator, but we asked whether it also acts as a tumor promoter once malignant initiation, such as caused by K-ras activation, has taken place...
  38. Kelly Spratt K, Philipp Staheli J, Gurley K, Hoon Kim K, Knoblaugh S, Kemp C. Inhibition of PI-3K restores nuclear p27Kip1 expression in a mouse model of Kras-driven lung cancer. Oncogene. 2009;28:3652-62 pubmed publisher
    ..Urethane-induced lung tumors in mice frequently harbor mutations in the Kras oncogene, and in this study, we use this model to address the regulation of p27 during tumorigenesis...
  39. Hanlon L, Avila J, Demarest R, Troutman S, Allen M, Ratti F, et al. Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Res. 2010;70:4280-6 pubmed publisher
    K-ras is the most commonly mutated oncogene in pancreatic cancer and its activation in murine models is sufficient to recapitulate the spectrum of lesions seen in human pancreatic ductal adenocarcinoma (PDAC)...
  40. Regala R, Davis R, Kunz A, Khoor A, Leitges M, Fields A. Atypical protein kinase C{iota} is required for bronchioalveolar stem cell expansion and lung tumorigenesis. Cancer Res. 2009;69:7603-11 pubmed publisher
    ..To address this question, we established a mouse model in which oncogenic Kras(G12D) is activated by Cre-mediated recombination in the lung with or without simultaneous genetic loss of the mouse ..
  41. Braun B, Tuveson D, Kong N, Le D, Kogan S, Rozmus J, et al. Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proc Natl Acad Sci U S A. 2004;101:597-602 pubmed
    b>RAS mutations are common in myeloid malignancies; however, it is not known whether oncogenic RAS can initiate leukemia...
  42. CARRIERE C, Seeley E, Goetze T, Longnecker D, Korc M. The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia. Proc Natl Acad Sci U S A. 2007;104:4437-42 pubmed
    ..in pancreatic ductal adenocarcinoma (PDAC), we generated a mouse model in which endogenous expression of mutated Kras (Kras(G12D)) was initially directed to a population of pancreatic exocrine progenitors characterized by the ..
  43. Molina Arcas M, Hancock D, Sheridan C, Kumar M, Downward J. Coordinate direct input of both KRAS and IGF1 receptor to activation of PI3 kinase in KRAS-mutant lung cancer. Cancer Discov. 2013;3:548-63 pubmed publisher
    ..lung cancer (NSCLC) lines, we show here that MAP-ERK kinase (MEK) and RAF inhibitors are selectively toxic for the KRAS-mutant genotype, whereas phosphoinositide 3-kinase (PI3K), AKT, and mTOR inhibitors are not...
  44. Morton J, Jamieson N, Karim S, Athineos D, Ridgway R, Nixon C, et al. LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest. Gastroenterology. 2010;139:586-97, 597.e1-6 pubmed publisher
    ..We have identified a novel LKB1-p21 axis that suppresses PDAC following Kras mutation in vivo...
  45. Besmer D, Curry J, Roy L, Tinder T, Sahraei M, Schettini J, et al. Pancreatic ductal adenocarcinoma mice lacking mucin 1 have a profound defect in tumor growth and metastasis. Cancer Res. 2011;71:4432-42 pubmed publisher
    ..This is the first study to utilize a Muc1-null PDA mouse to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. ..
  46. Junttila M, Karnezis A, Garcia D, Madriles F, Kortlever R, Rostker F, et al. Selective activation of p53-mediated tumour suppression in high-grade tumours. Nature. 2010;468:567-71 pubmed publisher
    ..Deregulation of the Ras pathway is a frequent hallmark of NSCLC, often through mutations that directly activate Kras. p53 is also frequently inactivated in NSCLC and, because oncogenic Ras can be a potent trigger of p53 (ref...
  47. Mills L, Zhang Y, Marler R, Herreros Villanueva M, Zhang L, Almada L, et al. Loss of the transcription factor GLI1 identifies a signaling network in the tumor microenvironment mediating KRAS oncogene-induced transformation. J Biol Chem. 2013;288:11786-94 pubmed publisher
    Although the biological role of KRAS is clearly established in carcinogenesis, the molecular mechanisms underlying this phenomenon are not completely understood...
  48. Gidekel Friedlander S, Chu G, Snyder E, Girnius N, Dibelius G, Crowley D, et al. Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell. 2009;16:379-89 pubmed publisher
    ..We show that a subpopulation of Pdx1-expressing cells is susceptible to oncogenic K-Ras-induced transformation without tissue injury, whereas insulin-expressing endocrine cells are completely refractory ..
  49. Meylan E, Dooley A, Feldser D, Shen L, Turk E, Ouyang C, et al. Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature. 2009;462:104-7 pubmed publisher
    ..Concomitant loss of p53 (also known as Trp53) and expression of oncogenic Kras(G12D) resulted in NF-kappaB activation in primary mouse embryonic fibroblasts...
  50. Ardito C, Grüner B, Takeuchi K, Lubeseder Martellato C, Teichmann N, Mazur P, et al. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell. 2012;22:304-17 pubmed publisher
    Initiation of pancreatic ductal adenocarcinoma (PDA) is definitively linked to activating mutations in the KRAS oncogene...
  51. Xu X, Rock J, Lu Y, Futtner C, Schwab B, Guinney J, et al. Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma. Proc Natl Acad Sci U S A. 2012;109:4910-5 pubmed publisher
    ..bronchoalveolar stem cell at the bronchioalveolar duct junction as a cancer cell of origin when a codon 12 K-Ras mutant is induced via adenoviral Cre inhalation...
  52. Mukhopadhyay A, Krishnaswami S, Yu B. Activated Kras alters epidermal homeostasis of mouse skin, resulting in redundant skin and defective hair cycling. J Invest Dermatol. 2011;131:311-9 pubmed publisher
    ..in HRAS are associated with the vast majority of patients with Costello syndrome, mutations in its paralog, KRAS, are rare...
  53. Kompier L, Lurkin I, van der Aa M, van Rhijn B, van der Kwast T, Zwarthoff E. FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy. PLoS ONE. 2010;5:e13821 pubmed publisher
    ..these issues, we developed a mutation assay for the simultaneous detection of 19 possible mutations in the HRAS, KRAS, and NRAS genes...
  54. Murphy D, Junttila M, Pouyet L, Karnezis A, Shchors K, Bui D, et al. Distinct thresholds govern Myc's biological output in vivo. Cancer Cell. 2008;14:447-57 pubmed publisher
    ..The requirement to keep activated oncogenes at a low level to avoid engaging tumor suppression is likely an important selective pressure governing the early stages of tumor microevolution. ..
  55. Feng Y, Bommer G, Zhao J, Green M, Sands E, Zhai Y, et al. Mutant KRAS promotes hyperplasia and alters differentiation in the colon epithelium but does not expand the presumptive stem cell pool. Gastroenterology. 2011;141:1003-1013.e1-10 pubmed publisher
    ..Mutations in KRAS are found in ?40% of CRCs and large adenomas and a subset of HPPs...
  56. Corcoran R, Contino G, Deshpande V, Tzatsos A, Conrad C, Benes C, et al. STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Res. 2011;71:5020-9 pubmed publisher
    ..functions of STAT3 in vivo, we developed mouse models that test the impact of conditional inactivation of STAT3 in KRAS-driven PDAC...
  57. James R, Arends M, Plowman S, Brooks D, Miles C, West J, et al. K-ras proto-oncogene exhibits tumor suppressor activity as its absence promotes tumorigenesis in murine teratomas. Mol Cancer Res. 2003;1:820-5 pubmed
    b>Ras proteins transduce signals from membrane-bound receptors via multiple downstream effector pathways and thereby affect fundamental cellular processes, including proliferation, apoptosis, and differentiation...
  58. Zhang N, Bai H, David K, Dong J, Zheng Y, Cai J, et al. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell. 2010;19:27-38 pubmed publisher
    ..Our studies link Merlin/NF2 to mammalian Hippo signaling and implicate YAP activation as a mediator of pathologies relevant to Neurofibromatosis 2...
  59. Kindler T, Cornejo M, Scholl C, Liu J, Leeman D, Haydu J, et al. K-RasG12D-induced T-cell lymphoblastic lymphoma/leukemias harbor Notch1 mutations and are sensitive to gamma-secretase inhibitors. Blood. 2008;112:3373-82 pubmed publisher
    To study the impact of oncogenic K-Ras on T-cell leukemia/lymphoma development and progression, we made use of a conditional K-Ras(G12D) murine knockin model, in which oncogenic K-Ras is expressed from its endogenous promoter...
  60. Kopp J, von Figura G, Mayes E, Liu F, Dubois C, Morris J, et al. Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell. 2012;22:737-50 pubmed publisher
    ..ductal adenocarcinoma (PDA), we labeled and traced pancreatic cell populations after induction of a PDA-initiating Kras mutation...
  61. Navas C, Hernández Porras I, Schuhmacher A, Sibilia M, Guerra C, Barbacid M. EGF receptor signaling is essential for k-ras oncogene-driven pancreatic ductal adenocarcinoma. Cancer Cell. 2012;22:318-30 pubmed publisher
    ..evidence indicates that mutation/activation of EGF receptors (EGFRs) is mutually exclusive with the presence of K-RAS oncogenes in lung and colon tumors. We have validated these observations using genetically engineered mouse models...
  62. Kojima K, Vickers S, Adsay N, Jhala N, Kim H, Schoeb T, et al. Inactivation of Smad4 accelerates Kras(G12D)-mediated pancreatic neoplasia. Cancer Res. 2007;67:8121-30 pubmed
    ..Activating mutations in KRAS are almost uniformly present in early-stage disease, with subsequent inactivating mutations in p16(INK4A), p53, and ..
  63. Chan I, Kutok J, Williams I, Cohen S, Kelly L, Shigematsu H, et al. Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. J Clin Invest. 2004;113:528-38 pubmed
    Oncogenic ras alleles are among the most common mutations found in patients with acute myeloid leukemia (AML)...
  64. Maraver A, Fernandez Marcos P, Herranz D, Muñoz Martin M, Gomez Lopez G, Canamero M, et al. Therapeutic effect of ?-secretase inhibition in KrasG12V-driven non-small cell lung carcinoma by derepression of DUSP1 and inhibition of ERK. Cancer Cell. 2012;22:222-34 pubmed publisher
    Here, we have investigated the role of the Notch pathway in the generation and maintenance of Kras(G12V)-driven non-small cell lung carcinomas (NSCLCs)...
  65. Schepers A, Snippert H, Stange D, van den Born M, van Es J, van de Wetering M, et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science. 2012;337:730-5 pubmed publisher
    ..The Lgr5(+) cells are intermingled with Paneth cells near the adenoma base, a pattern reminiscent of the architecture of the normal crypt niche...
  66. Laconti J, Shivapurkar N, Preet A, Deslattes Mays A, Peran I, Kim S, et al. Tissue and serum microRNAs in the Kras(G12D) transgenic animal model and in patients with pancreatic cancer. PLoS ONE. 2011;6:e20687 pubmed publisher
    ..expression patterns during progression of normal tissues to invasive pancreatic adenocarcinoma in the p48-Cre/LSL-Kras(G12D) mouse model mirrors the miR changes observed in human pancreatic cancer tissues...
  67. Gao Q, Steine E, Barrasa M, Hockemeyer D, Pawlak M, Fu D, et al. Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression. Proc Natl Acad Sci U S A. 2011;108:18061-6 pubmed publisher
    ..Our results suggest that Dnmt3a may act like a tumor-suppressor gene in lung tumor progression and may be a critical determinant of lung cancer malignancy. ..
  68. Maniati E, Bossard M, Cook N, Candido J, Emami Shahri N, Nedospasov S, et al. Crosstalk between the canonical NF-?B and Notch signaling pathways inhibits Ppar? expression and promotes pancreatic cancer progression in mice. J Clin Invest. 2011;121:4685-99 pubmed publisher
    The majority of human pancreatic cancers have activating mutations in the KRAS proto-oncogene. These mutations result in increased activity of the NF-?B pathway and the subsequent constitutive production of proinflammatory cytokines...
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    ..Here we modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS and inactivation of the p53 pathway, using conditional alleles in mice...
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    ..PanIN-3) as the cells attain molecular alterations to key regulatory genes, including activating mutations in the KRAS protooncogene...
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    ..Here we report that the major function of glucose metabolism for Kras-induced anchorage-independent growth, a hallmark of transformed cells, is to support the pentose phosphate pathway...
  73. Kim C, Jackson E, Woolfenden A, Lawrence S, Babar I, Vogel S, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005;121:823-35 pubmed
    ..Furthermore, BASCs expanded in response to oncogenic K-ras in culture and in precursors of lung tumors in vivo...
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    Activating KRAS mutations and p16(Ink4a) inactivation are near universal events in human pancreatic ductal adenocarcinoma (PDAC)...
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    ..endometriosis and endometrioid ovarian adenocarcinoma in mice, both based on the activation of an oncogenic K-ras allele...
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    ..Furthermore, although some oncogenic (Kras, Pten/PI3K and Trp53) pathways that are frequently mutated, deleted or amplified in ovarian cancer are known, how ..
  78. Hingorani S, Wang L, Multani A, Combs C, Deramaudt T, Hruban R, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 2005;7:469-83 pubmed
    ..for pancreatic ductal adenocarcinoma (PDA), we have targeted concomitant endogenous expression of Trp53(R172H) and Kras(G12D) to the mouse pancreas, revealing the cooperative development of invasive and widely metastatic carcinoma that ..
  79. DuPage M, Dooley A, Jacks T. Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase. Nat Protoc. 2009;4:1064-72 pubmed publisher
    ..in two conditional genetic models of human non-small cell lung cancer (NSCLC) using the activation of oncogenic K-ras alone or in combination with the loss of function of p53...
  80. Bardeesy N, Cheng K, Berger J, Chu G, Pahler J, Olson P, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 2006;20:3130-46 pubmed
    ..PDAC) with concurrent mutational inactivation of the INK4A/ARF tumor suppressor locus and activation of the KRAS oncogene...
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    ..Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer...
  82. Iwanaga K, Yang Y, Raso M, Ma L, Hanna A, Thilaganathan N, et al. Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer. Cancer Res. 2008;68:1119-27 pubmed publisher
    ..no discernible effect on bronchial epithelial histology, it accelerated lung tumorigenesis initiated by oncogenic K-ras, causing more rapid lethality than that induced by oncogenic K-ras alone (8 weeks versus 24 weeks of median ..
  83. Yang Y, Iwanaga K, Raso M, Wislez M, Hanna A, Wieder E, et al. Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer. PLoS ONE. 2008;3:e2220 pubmed publisher
    ..Bronchioalveolar stem cells (BASCs) are a putative cancer stem cell population in mouse models of oncogenic K-ras-induced lung adenocarcinoma, an histologic subtype of NSCLC...
  84. Chiang M, Xu L, Shestova O, Histen G, L Heureux S, Romany C, et al. Leukemia-associated NOTCH1 alleles are weak tumor initiators but accelerate K-ras-initiated leukemia. J Clin Invest. 2008;118:3181-94 pubmed publisher
    ..weak gain-of-function NOTCH1 alleles accelerated the onset of leukemia initiated by constitutively active K-ras and gave rise to tumors that were sensitive to Notch signaling pathway inhibition...
  85. Vernon P, Loux T, Schapiro N, Kang R, Muthuswamy R, Kalinski P, et al. The receptor for advanced glycation end products promotes pancreatic carcinogenesis and accumulation of myeloid-derived suppressor cells. J Immunol. 2013;190:1372-9 pubmed publisher
    ..To study the role of RAGE expression in the setting of mutant Ras-promoted pancreatic carcinogenesis (KC), a triple-transgenic model of spontaneous murine PDA in a RAGE-null ..
  86. Shakya R, Gonda T, Quante M, Salas M, Kim S, Brooks J, et al. Hypomethylating therapy in an aggressive stroma-rich model of pancreatic carcinoma. Cancer Res. 2013;73:885-96 pubmed publisher
    ..These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy. ..
  87. Daniluk J, Liu Y, Deng D, Chu J, Huang H, Gaiser S, et al. An NF-?B pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice. J Clin Invest. 2012;122:1519-28 pubmed publisher
    Genetic mutations that give rise to active mutant forms of Ras are oncogenic and found in several types of tumor. However, such mutations are not clear biomarkers for disease, since they are frequently detected in healthy individuals...
  88. White A, Tran K, Khuu J, Dang C, Cui Y, Binder S, et al. Defining the origins of Ras/p53-mediated squamous cell carcinoma. Proc Natl Acad Sci U S A. 2011;108:7425-30 pubmed publisher
    ..Furthermore, we provide insights into the inability of hair follicle TA cells to respond to tumorigenic stimuli. ..
  89. Young N, Crowley D, Jacks T. Uncoupling cancer mutations reveals critical timing of p53 loss in sarcomagenesis. Cancer Res. 2011;71:4040-7 pubmed publisher
    ..By integrating a Flp-inducible allele of K-ras(G12D) with established methods for Cre-mediated p53 deletion, we were able to separately control the mutation of ..
  90. Zaslavsky A, Baek K, Lynch R, Short S, Grillo J, Folkman J, et al. Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis. Blood. 2010;115:4605-13 pubmed publisher
    ..Further, this work implicates the use of thrombospondin-1 levels in platelets as an indicator of tumor growth and regression. ..
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    To investigate the role of an activated K-Ras gene in the initiation and maintenance of lung adenocarcinomas, we developed transgenic mice that express murine K-Ras4b(G12D) under the control of doxycycline in type II pneumocytes...