Gene Symbol: Tgfa
Description: transforming growth factor alpha
Alias: RATTGFAA, TGFAA, protransforming growth factor alpha
Species: rat
Products:     Tgfa

Top Publications

  1. Lee D, Rose T, Webb N, Todaro G. Cloning and sequence analysis of a cDNA for rat transforming growth factor-alpha. Nature. 1985;313:489-91 pubmed
  2. Hardie W, Bejarano P, Miller M, Yankaskas J, Ritter J, Whitsett J, et al. Immunolocalization of transforming growth factor alpha and epidermal growth factor receptor in lungs of patients with cystic fibrosis. Pediatr Dev Pathol. 1999;2:415-23 pubmed
  3. Rosen K, Coll M, Li A, Filmus J. Transforming growth factor-alpha prevents detachment-induced inhibition of c-Src kinase activity, Bcl-XL down-regulation, and apoptosis of intestinal epithelial cells. J Biol Chem. 2001;276:37273-9 pubmed
    ..We conclude that TGF-alpha has the ability to suppress anoikis of intestinal epithelial cells, at least in part, by reverting the loss of c-Src activity and Bcl-X(L) expression induced by detachment from the ECM. ..
  4. Wang Y, Asselin E, Tsang B. Involvement of transforming growth factor alpha in the regulation of rat ovarian X-linked inhibitor of apoptosis protein expression and follicular growth by follicle-stimulating hormone. Biol Reprod. 2002;66:1672-80 pubmed
  5. Massague J. Epidermal growth factor-like transforming growth factor. I. Isolation, chemical characterization, and potentiation by other transforming factors from feline sarcoma virus-transformed rat cells. J Biol Chem. 1983;258:13606-13 pubmed
    ..4-kDa eTGF and a second 14-kDa transforming factor(s). ..
  6. Li C, Hao M, Cao Z, Ding W, Graves Deal R, Hu J, et al. Naked2 acts as a cargo recognition and targeting protein to ensure proper delivery and fusion of TGF-alpha containing exocytic vesicles at the lower lateral membrane of polarized MDCK cells. Mol Biol Cell. 2007;18:3081-93 pubmed
  7. Luetteke N, Qiu T, Fenton S, Troyer K, Riedel R, Chang A, et al. Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development. Development. 1999;126:2739-50 pubmed
    ..Finally, the additional loss of growth factors from pups nursed by triple null dams further worsened their survival and growth, establishing functions for both maternal- and neonatal-derived growth factors. ..
  8. Marchio S, Lahdenranta J, Schlingemann R, Valdembri D, Wesseling P, Arap M, et al. Aminopeptidase A is a functional target in angiogenic blood vessels. Cancer Cell. 2004;5:151-62 pubmed
    ..Finally, we successfully treated tumor-bearing mice with APA binding peptides or anti-APA blocking monoclonal antibodies. These data show that APA is a regulator of blood vessel formation, and can serve as a functional vascular target. ..
  9. Wong H, Lemoine N. Pancreatic cancer: molecular pathogenesis and new therapeutic targets. Nat Rev Gastroenterol Hepatol. 2009;6:412-22 pubmed publisher
    ..This Review describes some of the important developments and targeted agents for pancreatic cancer that have been tested in clinical trials. ..

More Information


  1. Kitano M, Wada J, Ariki Y, Kato M, Wanibuchi H, Morimura K, et al. Possible tumor development from double positive foci for TGF-alpha and GST-P observed in early stages on rat hepatocarcinogenesis. Cancer Sci. 2006;97:478-83 pubmed
    ..Our data suggest that double positive foci for GST-P and TGF-alpha in the early stages of rat hepatocarcinogenesis may develop into tumors with promotion. ..
  2. Grasl Kraupp B, Schausberger E, Hufnagl K, Gerner C, Löw Baselli A, Rossmanith W, et al. A novel mechanism for mitogenic signaling via pro-transforming growth factor alpha within hepatocyte nuclei. Hepatology. 2002;35:1372-80 pubmed
  3. Sukhotnik I, Shteinberg D, Ben Lulu S, Bashenko Y, Mogilner J, Ure B, et al. Transforming growth factor-alpha stimulates enterocyte proliferation and accelerates intestinal recovery following methotrexate-induced intestinal mucositis in a rat and a cell culture model. Pediatr Surg Int. 2008;24:1303-11 pubmed publisher
    ..These observations may have significant implications for the treatment of patients on chemotherapy who develop severe mucositis. ..
  4. Lee C. Transforming growth factor alpha immunoreactivity in human gallbladder and extrahepatic biliary tract tumours. Eur J Surg Oncol. 1998;24:38-42 pubmed
    ..Correlation was found between TGF-alpha and EFGR expression in gallbladder and biliary tract tumours. ..
  5. Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchier M, Beger H. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Invest. 1992;90:1352-60 pubmed
  6. Nie S, Sun H, Wu X, Qian X. Cyclooxygenase 2, pS2, inducible nitric oxide synthase and transforming growth factor alpha in gastric adaptation to stress. World J Gastroenterol. 2004;10:3537-41 pubmed
    ..These changes play an important role in adaptation of gastric mucosa after repeated WRS. ..
  7. Li C, Franklin J, Graves Deal R, Jerome W, Cao Z, Coffey R. Myristoylated Naked2 escorts transforming growth factor alpha to the basolateral plasma membrane of polarized epithelial cells. Proc Natl Acad Sci U S A. 2004;101:5571-6 pubmed
    ..These data identify an unexpected function for NKD2, i.e., myristoylation-dependent escort of TGF alpha to the basolateral plasma membrane of polarized epithelial cells. ..
  8. Gschwind A, Hart S, Fischer O, Ullrich A. TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells. EMBO J. 2003;22:2411-21 pubmed
    ..Thus, TACE can function as an effector of GPCR-mediated signalling and represents a key element of the cellular receptor cross-talk network. ..
  9. Borrell Pages M, Fernandez Larrea J, Borroto A, Rojo F, Baselga J, Arribas J. The carboxy-terminal cysteine of the tetraspanin L6 antigen is required for its interaction with SITAC, a novel PDZ protein. Mol Biol Cell. 2000;11:4217-25 pubmed
    ..In summary, the characterization of the protein SITAC has unveiled novel sequences recognized by PDZ domains, and it suggests that L6A is a natural ligand of this PDZ protein. ..
  10. Jiang D, Yang H, Willson J, Liang J, Humphrey L, Zborowska E, et al. Autocrine transforming growth factor alpha provides a growth advantage to malignant cells by facilitating re-entry into the cell cycle from suboptimal growth states. J Biol Chem. 1998;273:31471-9 pubmed
  11. Naito K, Moteki H, Kimura M, Natsume H, Ogihara M. Serotonin 5-HT2B Receptor-Stimulated DNA Synthesis and Proliferation Are Mediated by Autocrine Secretion of Transforming Growth Factor-α in Primary Cultures of Adult Rat Hepatocytes. Biol Pharm Bull. 2016;39:570-7 pubmed publisher
    ..These results indicate that the proliferative mechanism of action of 5-HT is mediated mainly through a 5-HT2B receptor/Gq/PLC-stimulated increase in autocrine secretion of TGF-α from primary cultured hepatocytes. ..
  12. Pavelic K, Hrascan R, Kapitanovic S, Vranes Z, Cabrijan T, Spaventi S, et al. Molecular genetics of malignant insulinoma. Anticancer Res. 1996;16:1707-17 pubmed
  13. Singh A, Harris R. Autocrine, paracrine and juxtacrine signaling by EGFR ligands. Cell Signal. 2005;17:1183-93 pubmed
    ..In this review, we discuss the different ways that EGFR ligands can activate the receptor and the possible biological implications. ..
  14. Hise M, Salmanullah M, Liu L, Drachenberg C, Papadimitriou J, Rohan R. Control of the epidermal growth factor receptor and its ligands during renal injury. Nephron. 2001;88:71-9 pubmed
    ..Multiple EGF-like ligands may be important in activating the upregulated EGF receptor during repair from renal injury. ..
  15. Dell K, Nemo R, Sweeney W, Levin J, Frost P, Avner E. A novel inhibitor of tumor necrosis factor-alpha converting enzyme ameliorates polycystic kidney disease. Kidney Int. 2001;60:1240-8 pubmed
    ..These findings support the pathophysiological role of the TGF-alpha/EGFR axis in murine ARPKD and demonstrate that inhibition of TGF-alpha secretion has therapeutic potential in PKD. ..
  16. Petegnief V, Friguls B, Sanfeliu C, Suñol C, Planas A. Transforming growth factor-alpha attenuates N-methyl-D-aspartic acid toxicity in cortical cultures by preventing protein synthesis inhibition through an Erk1/2-dependent mechanism. J Biol Chem. 2003;278:29552-9 pubmed
  17. Riese D, Kim E, Elenius K, Buckley S, Klagsbrun M, Plowman G, et al. The epidermal growth factor receptor couples transforming growth factor-alpha, heparin-binding epidermal growth factor-like factor, and amphiregulin to Neu, ErbB-3, and ErbB-4. J Biol Chem. 1996;271:20047-52 pubmed
    ..Therefore, EGF, TGF-alpha, AR, and HB-EGF are functionally identical in this model system and behave differently from the EGF family hormones betacellulin and neuregulins. ..
  18. Kimura M, Okamoto H, Natsume H, Ogihara M. IP receptor agonist-induced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes: the involvement of endogenous transforming growth factor-alpha. J Pharmacol Sci. 2009;109:618-29 pubmed
    ..These results indicate that the IP receptor agonist-induced hepatocyte mitogenesis is mediated by autocrine secretion of TGF-alpha followed by activation of a receptor tyrosine kinase / ERK pathway. ..
  19. Millena A, Reddy S, Bowling G, Khan S. Autocrine regulation of steroidogenic function of Leydig cells by transforming growth factor-alpha. Mol Cell Endocrinol. 2004;224:29-39 pubmed
    ..A PKA inhibitor (H89) blocked both TGFalpha and LH effects on steroidogenesis. We conclude that TGFalpha plays an autocrine role in LH dependent development and function of Leydig cells. ..
  20. Yu X, Zhu S, Xu Z, Hu X, Zhu T, Chen J, et al. Roles of EGFR-Stat3 signal pathway in carcinogenesis of experimental hepatoma in rats. J Cancer Res Clin Oncol. 2007;133:145-52 pubmed
    ..TGFalpha-EGFR autocrine ring formation may lead to the activation of Stat3 and in turn, promote proliferation and regulate the transcription of genes regulating cell apoptosis and cell cycle...
  21. Buck M, Poli V, van der Geer P, Chojkier M, Hunter T. Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBP beta is required for hepatocyte proliferation induced by TGF alpha. Mol Cell. 1999;4:1087-92 pubmed
    ..Thus, a site-specific phosphorylation of the transcription factor C/EBP beta is critical for hepatocyte proliferation induced by TGF alpha and other stimuli that activate RSK. ..
  22. Akkoyunlu G, Demir R, Ustunel I. Distribution patterns of TGF-alpha, laminin and fibronectin and their relationship with folliculogenesis in rat ovary. Acta Histochem. 2003;105:295-301 pubmed
    ..As TGF-alpha is associated with follicles and their relationship with the extracellular matrix, TGF-alpha may also induce formation of basement membranes which contains laminin and fibronectin components. ..
  23. Madtes D, Rubenfeld G, Klima L, Milberg J, Steinberg K, Martin T, et al. Elevated transforming growth factor-alpha levels in bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1998;158:424-30 pubmed
    ..We conclude that increased levels of TGF-alpha in BALF are common in patients with ARDS and that lavage TGF-alpha is associated with a marker of the fibroproliferative response in sustained ARDS. ..
  24. Blasband A, Rogers K, Chen X, Azizkhan J, Lee D. Characterization of the rat transforming growth factor alpha gene and identification of promoter sequences. Mol Cell Biol. 1990;10:2111-21 pubmed
    ..In addition, they direct the expression of the bacterial chloramphenicol acetyltransferase gene in transient-transfection assays. ..
  25. Appleton C, Usmani S, Bernier S, Aigner T, Beier F. Transforming growth factor alpha suppression of articular chondrocyte phenotype and Sox9 expression in a rat model of osteoarthritis. Arthritis Rheum. 2007;56:3693-705 pubmed
    ..Seven OA samples showed TGFA mRNA levels similar to those in the normal controls, but expression was markedly increased in the other 5 OA ..
  26. Luetteke N, Lee D. Transforming growth factor alpha: expression, regulation and biological action of its integral membrane precursor. Semin Cancer Biol. 1990;1:265-75 pubmed
    ..Finally, overexpression of TGF alpha promoted neoplastic transformation of certain epithelia. In coagulation gland, there was dramatic hyperplasia and dysplasia with focal evidence of carcinoma in situ.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  27. Nomura S, Settle S, Leys C, Means A, Peek R, Leach S, et al. Evidence for repatterning of the gastric fundic epithelium associated with Ménétrier's disease and TGFalpha overexpression. Gastroenterology. 2005;128:1292-305 pubmed
    ..Overexpression of TGFalpha in MT-TGFalpha mice and Ménétrier's disease patients elicits ectopic expression in the fundus of Pdx1, consistent with the phenotype of antralization. ..
  28. Baughman R, Lower E, Miller M, Bejarano P, Heffelfinger S. Overexpression of transforming growth factor-alpha and epidermal growth factor-receptor in idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16:57-61 pubmed
    ..There was a small but significantly greater expression of EGF-R in the bronchial epithelium and type 2 pneumocytes of the IPF patients. TGF-alpha is overexpressed in patients with IPF, especially in the vascular endothelial cells. ..
  29. Dombrowski F, Bannasch P, Pfeifer U. Hepatocellular neoplasms induced by low-number pancreatic islet transplants in streptozotocin diabetic rats. Am J Pathol. 1997;150:1071-87 pubmed
    ..Hepatocarcinogenesis in this new animal model is probably due to the hormonal and growth-stimulating effects of insulin secreted by the intraportally transplanted islets of Langerhans in diabetic rats. ..
  30. Gentry L, Twardzik D, Lim G, Ranchalis J, Lee D. Expression and characterization of transforming growth factor alpha precursor protein in transfected mammalian cells. Mol Cell Biol. 1987;7:1585-91 pubmed
    ..These data show that these nontransformed BHK cells possess the ability to process the TGF alpha precursor molecule into its native form. ..
  31. Franklin J, Yoshiura K, Dempsey P, Bogatcheva G, Jeyakumar L, Meise K, et al. Identification of MAGI-3 as a transforming growth factor-alpha tail binding protein. Exp Cell Res. 2005;303:457-70 pubmed
  32. Le Cras T, Hardie W, Deutsch G, Albertine K, Ikegami M, Whitsett J, et al. Transient induction of TGF-alpha disrupts lung morphogenesis, causing pulmonary disease in adulthood. Am J Physiol Lung Cell Mol Physiol. 2004;287:L718-29 pubmed
    ..Transient induction of TGF-alpha during early alveologenesis permanently disrupted lung structure and function and caused chronic lung disease. ..
  33. Aihaiti X, Hayamizu K, Oishi K, Yoshimitsu M, Itamoto T, Asahara T. Facilitation of survival in a rat fulminant hepatic failure model by combination therapy using recombinant G-CSF and tacrolimus. J Interferon Cytokine Res. 2006;26:226-34 pubmed
    ..These results suggest that tacrolimus improves the hepatocyte replication and rHuG-CSF contributes to tissue reconstitution, and this combination therapy directly facilitates liver regeneration in the FHF model. ..
  34. Kim I, Mogford J, Chao J, Mustoe T. Wound epithelialization deficits in the transforming growth factor-alpha knockout mouse. Wound Repair Regen. 2001;9:386-90 pubmed
    ..The data further show the importance of appropriate wound models to address the role of vulnerary factors. ..
  35. Siveke J, Einwächter H, Sipos B, Lubeseder Martellato C, Kloppel G, Schmid R. Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN. Cancer Cell. 2007;12:266-79 pubmed
    Growth factors have been implicated in pancreatic carcinogenesis. In this study we analyzed the effect of Tgfa overexpression in addition to mutant Kras(G12D) by crossing Elastase-Tgfa mice with p48(+/Cre);Kras(+/LSL-G12D) mice...
  36. Wang Y, Maciejewski B, Soto Reyes D, Lee H, Warburton D, Sanchez Esteban J. Mechanical stretch promotes fetal type II epithelial cell differentiation via shedding of HB-EGF and TGF-alpha. J Physiol. 2009;587:1739-53 pubmed publisher
    ..These studies provide novel mechanistic information potentially relevant to fetal lung development and to mechanical ventilation-induced lung injury. ..
  37. Guerra Crespo M, Gleason D, Sistos A, Toosky T, Solaroglu I, Zhang J, et al. Transforming growth factor-alpha induces neurogenesis and behavioral improvement in a chronic stroke model. Neuroscience. 2009;160:470-83 pubmed publisher
  38. Luetteke N, Qiu T, Peiffer R, Oliver P, Smithies O, Lee D. TGF alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Cell. 1993;73:263-78 pubmed
    ..Crosses between wa-1 homozygotes and TGF alpha-targeted mice confirmed that wa-1 and TGF alpha are allelic. ..
  39. Garrett T, McKern N, Lou M, Elleman T, Adams T, Lovrecz G, et al. Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha. Cell. 2002;110:763-73 pubmed
    ..Based on sequence conservation, buried surface area, and mutagenesis experiments, the back-to-back dimer is favored to be biologically relevant. ..
  40. Tuli S, Liu R, Chen C, Blalock T, Goldstein M, Schultz G. Immunohistochemical localization of EGF, TGF-alpha, TGF-beta, and their receptors in rat corneas during healing of excimer laser ablation. Curr Eye Res. 2006;31:709-19 pubmed
    ..In addition, the proteins are primarily localized in basal layers of epithelial cells, which suggest these cells are active in synthesizing autocrine and paracrine growth factors that modulate corneal wound healing. ..
  41. Strachan L, Murison J, Prestidge R, Sleeman M, Watson J, Kumble K. Cloning and biological activity of epigen, a novel member of the epidermal growth factor superfamily. J Biol Chem. 2001;276:18265-71 pubmed
    ..Thus, Epigen is the newest member of the EGF superfamily and, with its ability to promote the growth of epithelial cells, may constitute a novel molecular target for wound-healing therapy. ..
  42. Marquardt H, Hunkapiller M, Hood L, Todaro G. Rat transforming growth factor type 1: structure and relation to epidermal growth factor. Science. 1984;223:1079-82 pubmed
    ..Production of this polypeptide by various neoplastic cells might contribute to the continued expression of the transformed phenotype. ..
  43. Ni W, Lin N, He H, Zhu J, Zhang Y. Lipopolysaccharide induces up-regulation of TGF-? through HDAC2 in a rat model of bronchopulmonary dysplasia. PLoS ONE. 2014;9:e91083 pubmed publisher
    ..Together, these findings indicate that attenuation of TGF-?-mediated effects in the lung by enhancing HDAC2 may have a therapeutic effect on treating BPD. ..