J E Visvader

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..Together, these findings suggest that deregulation of LMO4 in breast epithelium contributes directly to breast neoplasia by altering the rate of cellular proliferation and promoting cell invasion...

..Thus, mouse mammary stem cells were negative for ERalpha, PR, and ErbB2 and appeared to share common properties with poor-prognosis basal breast cancer...

..Although the CSC concept will have clinical relevance in specific cases, accumulating evidence suggests that it will be imperative to target all CSC subsets within the tumor to prevent relapse...

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..We hypothesized that germline mutations in FANCD2, BRIP1/BACH1, LMO4 and SFN may account for some of the unexplained multiple-case breast cancer families...

..Although this variant can result in a truncated ATM product, its clinical significance as a high-penetrance breast cancer allele or its role as a low-penetrance risk-modifier is controversial...

..The epithelial cell signatures were used to interrogate mouse models of mammary tumorigenesis and to compare with their normal human counterpart subsets to identify conserved genes and networks...

..Here we have explored a role for macrophages in regulating mammary stem cell (MaSC) activity, by assessing the ability of MaSCs to reconstitute a mammary gland in a macrophage-depleted fat pad...

..Here we investigated the influence of DEAF-1 on human and mouse mammary epithelial cells both in vitro and in vivo and identified a potential target gene...

..Here we review the characteristics of mouse mammary stem cells, their estrogen receptor status, and the potential cellular hierarchy that exists within the mammary gland...

..The clinical relevance of CSCs remains a fundamental issue but preliminary findings indicate that specific targeting may be possible...

..These studies imply a role for LMO4 in maintaining proliferation of mammary epithelium and suggest that deregulation of this gene may contribute to breast tumorigenesis...

..Potential relationships between normal epithelial populations and breast tumor subtypes are discussed, with implications for understanding the cellular etiology underpinning breast tumor heterogeneity...

..This review will discuss recent insights into the transcriptional networks important for mammary gland development and consider how deregulation of specific transcription factors contributes to the pathogenesis of breast cancer...

..This caveat should be considered when interpreting mammary reconstitution assays that incorporate Matrigel, particularly when transplanting high cell numbers...

..Here, we review the known characteristics of mammary stem and progenitor cells, their steroid receptor status, and the pathways that have thus far been implicated in regulating their self-renewal and differentiation...

..Our findings suggest that an aberrant luminal progenitor population is a target for transformation in BRCA1-associated basal tumors ...

..This review will summarize the strategy used in the identification of mouse mammary stem cells and their characterisation...

..These findings reveal a novel complex between BRCA1, LMO4, and CtIP and indicate a role for LMO4 as a repressor of BRCA1 activity in breast tissue...

..Furthermore, CPAP was found to augment Stat5-mediated transcription. Thus, we have identified CPAP as a novel coactivator of Stat5 proteins in the PRL (and probably other) pathways...

..The expression profile of Lmo4 suggests that this cofactor is an important regulator of epithelial proliferation and has implications for its role in the pathogenicity of cancer...

..Overall, our findings show the utility of the progenitor marker CD61 in the identification of CSCs that sustain specific mammary tumors...

..These findings reveal key roles for Notch signaling in MaSCs and luminal cell commitment and further suggest that inappropriate Notch activation promotes the self-renewal and transformation of luminal progenitor cells...

..These findings indicate a role for Taxreb107 as a lactogenic hormone-responsive gene during differentiation of the mammary gland...

..Thus, the primary mechanism by which LMO4 is deregulated in breast cancers appears to reflect overexpression of the gene rather than the acquisition of activating genetic mutations...

..Our data establish that single cells within the Lin-CD29hiCD24+ population are multipotent and self-renewing, properties that define them as MaSCs...

..Hypermethylation and silencing of specific SOCS genes in the ovary, and to a lesser extent in breast, may augment cytokine responsiveness in these tissues, thereby contributing to oncogenesis...

..Although many unresolved questions on CSCs remain, ongoing efforts to identify and characterize CSCs continue to be an important area of investigation, with the potential to identify novel tumor targeting strategies...

..In order to use adult epithelial SCs in regenerative medicine, we must additionally regulate their intrinsic properties to prevent (or enable) transdifferentiation in specified SC niches...

..Taken together, these data suggest that overexpression of this lipid-binding protein contributes to breast oncogenesis...

..These findings further indicate that breast cancer chemoprevention may be achieved, in part, through suppression of MaSC function...

..These studies provide evidence for the existence of an epithelial hierarchy within the mammary gland and establish Gata-3 as a critical regulator of luminal differentiation...

..Keratinocytes from mutant mice fail to "heal" in in vitro scratch assays, consistent with a general epidermal migratory defect that is dependent on ERK activation and actin cable formation...

..Thus, the use of a conditional targeting strategy has revealed that Lmo4 is required for proper development of the mammary gland during pregnancy and indicated that Lmo4 acts as a positive regulator of alveolar epithelial proliferation...

..This was accompanied by a ligand-induced increase in protein kinase B and Erk activation but not that of Stat5a. Phosphorylation of the receptor on Thr391 may therefore provide a new mechanism by which prolactin signaling is attenuated...

..Thus, overexpression of the LMO4 gene in breast cancer cells reflects increased promoter activity and appears to involve aberrant activation of the second promoter in a subset of these cells...

..Interestingly, these lipid binding and transfer specificities distinguish StarD10 from the related START domain proteins Pctp and CERT, suggesting a distinct biological function...

..Methods that rely on permutation of probes unrealistically assume independence of genes, while those that rely on permutation of sample are suitable only for two-group comparisons with a good number of replicates in each group...

..Our data establish Socs3 as a critical attenuator of pro-apoptotic pathways that act in the developing mammary gland and provide evidence that c-myc regulates apoptosis during involution...

..The accumulating data point to a complex network of signal transduction pathways that synergize to regulate apoptosis in the involuting mammary gland...

..Overall, these studies identify GATA-3 as an important regulator of tumor initiation through its ability to promote the differentiation of committed luminal progenitor cells...

..These findings suggest a role for FADD in maintaining the survival of mammary secretory alveolar cells after the establishment of lactation...

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..Thus, Socs2 and Elf5 are key members of the set of prolactin-regulated genes that mediate prolactin-driven mammary development...

..Thus Elf5 specifies the differentiation of CD61+ progenitors to establish the secretory alveolar lineage during pregnancy, providing a link between prolactin, transcriptional events, and alveolar development...

..Thus, free-flow electrophoresis is a powerful high-capacity complementary technique to RP-HPLC and SDS-PAGE for the purification of proteins from complex cell lysates...

..These findings constitute the first molecular definition of LIM-mediated protein-protein interactions and suggest a mechanism by which ldb1 can bind a variety of LIM domains that share low sequence homology...

..The delineation of this region reveals some specific differences when compared to the equivalent LMO4:Ldb1 interaction that hold promise for the development of reagents to specifically bind LMO2 in the treatment of leukemia...

..These combined properties provide a mechanism for the binding of Ldb1 to numerous LMO and LIM-HD proteins. Furthermore, the modular extended interface may form a general mode of binding to tandem LIM domains...

..Our data demonstrate the versatility of cZFs and have implications for the analysis of many as yet uncharacterized cZF proteins...

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..Our data indicate an important role for these two transcriptional regulators in pathways affecting neural tube closure and skeletal patterning, most likely reflecting their presence in a functional complex in vivo...

..These results suggest a specific model for CtIP homodimerization via its N terminus and contribute to an improved understanding of how this protein might assemble other factors required for its role as a transcriptional corepressor...

..3 and 1.7 A resolution, respectively. Anomalous Patterson maps calculated with data collected at the peak wavelength show strong peaks sufficient to determine the positions of four Zn atoms per asymmetric unit...

..Perturbation of this pathway leads to an increase in the levels of c-myc and its likely target genes, p53, bax and E2F-1, providing evidence that c-myc is a central effector of apoptosis during involution...