Jeffrey Rosen

..The functional importance of some of these factors in mammary gland development and milk protein gene expression has been elucidated by studying mice in which some of these factors have been deleted...

..Thus, C/EBPbeta appears to play a role in the specification of progenitor cell fate not only in the mammary gland, but also in a number of other tissues...

..Additionally, the expression level of FOXC1, another EMT inducer, correlates strongly with poor survival of breast cancer patients...

..With the new tools for epigenomics developed in recent years, we now can begin to establish a framework for the role of epigenetics in mammary gland development and disease...

..These data indicate that acute iFGFR1 signaling results in increased lateral budding of the mammary ductal epithelium, and that sustained activation induces alveolar hyperplasia and invasive lesions...

..The conserved regions might have biological importance for the regulation of genes in this genomic "neighborhood."..

..Furthermore, this p53-null mouse mammary tumor model may allow us to identify new CSC markers and to test the functional importance of these markers...

..Thus, the developmental heterogeneity of different breast cancers is in part a consequence of differential effects of oncogenes on distinct cell types in the breast...

..Recent studies signify a dramatic advance in our understanding of this phenomenon, and indicate a 'cell fate' model for parity-related changes that lead to protection against breast cancer...

..Further, they reveal protein translation initiation factors as potential therapeutic targets for human breast cancers with alterations in FGF signaling...

..Collectively, these data suggest a model for the assembly of a multiprotein complex that helps to define how the signaling pathways controlled by these lactogenic hormones are integrated to regulate beta-casein gene expression...

..These data demonstrate that, compared with differentiated cells, progenitor cells have different cell survival properties that may facilitate the development of targeted antiprogenitor cell therapies...

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..Additionally, in normal mouse MECs, high expression of miR-205 was observed in stem-cell-enriched cell populations isolated by FACS using established cell-surface markers...

..These findings show that inflammatory cells, specifically macrophages, are critical for mediating early events in an inducible transgenic mouse model of preneoplastic progression...

..These findings have critical implications for understanding both stem cell biology and the etiology of different breast cancer subtypes...

..This study illustrates the importance of beta-catenin signalling in mammary lobuloalveolar development...

..Thus, the heterogeneity of different breast cancers may reflect the activation of different oncogenic pathways, different cellular targets in which these genetic changes occur, or both...

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..These studies demonstrate, for the first time, that the duration of downstream signaling determines the distinct phenotypes mediated by very homologous RTKs in three-dimensional cultures...

..the models commonly used to investigate breast cancer including cell lines, xenografts and genetically engineered mice, are discussed to help address the question: what is the most powerful way to investigate this heterogeneous disease?..

..Here we review recent studies on the involvement of hormone receptors and several transcription factors in mammary stem/progenitor cell differentiation and lineage commitment...

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..Collectively, these data suggest that the communication between these regulatory regions with intervening DNA looping is a crucial step required to both create and maintain active chromatin domains and regulate transcription...

..Targeting proteins involved in EMT may provide a therapeutic strategy for eliminating surviving cells to prevent recurrence and improve long-term survival in breast cancer patients...

..These data demonstrate that precise control of p190-B Rho GTPase-activating protein activity is critical for normal branching morphogenesis during mammary gland development...

..This suggests that additional tumor-related events specifically influence the ability of the variant p53(R172L) molecule to inhibit tumor growth. These studies support gene therapy strategies employing specific p53 variants...

..Collectively, these changes prevent C/EBPbeta-null mammary epithelial cells from responding to hormone-induced proliferative signals...

..Finally, the Sca-1(pos) population is enriched for functional stem/progenitor cells, as demonstrated by its increased regenerative potential compared with Sca-1(neg) cells when transplanted into the cleared mammary fat pads of host mice...

..Together, these data suggest that C/EBPbeta is a master regulator of mammary epithelial cell fate and that the correct spatial pattern of PR and PrlR expression is a critical determinant of hormone-regulated cell proliferation...

..The addition of a pan MMP inhibitor abolished these phenotypes but did not prevent the effects of iFGFR1 on cell proliferation or survival...

..P190B is required for mammary gland morphogenesis, and overexpression of p190B in the mammary gland induces hyperplastic lesions. Hence, we hypothesized that p190B may play a pivotal role in mammary tumorigenesis...

..This model would appear an excellent one to test the effects of chemopreventive agents on the development of both ER-negative and ER-positive mammary tumors...

..These studies support the hypothesis that observed changes in the FGFR axis in mammals during CaP progression are causally important...

..These studies suggest that MR may compensate for the absence of GR at some, but not at all stages of mammary gland development...

..Here, we review recent evidence of the involvement of EMT in breast cancer TICs, focusing on clinical studies...

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..This is one of the first reports describing the functional properties of a large, developmentally regulated, mammalian, noncoding RNA...

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..In conclusion, microarray gene profiling suggests that MG-SPs are a lineage-deficient mammary gland subpopulation expressing key genes involved in cell cycle regulation, development, and angiogenesis...

..Therefore, inappropriate regulation of Chk1 levels during cell cycle progression will result in failed cell division and enhanced genomic instability...

..Together, these results suggest that p190-B regulates ductal morphogenesis, at least in part, by modulating the IGF signaling axis...

..Thus, depending on the signal transduction pathway responsible for activation, different conformations of activated Stat5 may result in selective biological responses...

..Thus, these results suggest that pretreatment with Akt inhibitors before ionizing radiation treatment may be of potential therapeutic benefit to patients...

..These data suggest that CDK2 phosphorylates histone H1 in vivo, resulting in a more open chromatin structure by destabilizing H1-chromatin interactions...

..Surprisingly, these effects appear to be specific for Chk1, but not Chk2, which may explain the recently reported in vivo haploinsufficiency phenotype observed in the mammary gland using a Chk1 conditional mouse model...

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..Collectively, these results suggest that maspin is part of the supramolecular structure of the adhesion plaque and it modulates cell adhesion via a beta1 integrin-dependent mechanism...

..The COMMA-Dbeta-geo cell line may provide a useful model to study the signaling pathways that control mammary progenitor cell regulation...

..Thus, Chk1 heterozygosity results in three distinct haploinsufficient phenotypes that can contribute to tumorigenesis: inappropriate S phase entry, accumulation of DNA damage during replication, and failure to restrain mitotic entry...

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..These studies implicate a critical role for amphiregulin in mammary stem cell differentiation as well as breast cancer initiation and progression...

..These results indicate that IGF signaling through p190-B and IRS proteins is critical for mammary bud formation and ensuing epithelial-mesenchymal interactions necessary to sustain mammary bud morphogenesis...

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..These results define a negative cross talk between PR and Stat5a/GR that may contribute to the physiological role of progesterone to repress lactogenic hormone induction of the beta-casein gene in the mammary gland during pregnancy...

..Taken together, our results demonstrate that Jak2 is a critical tyrosine kinase that conveys intracellular signals necessary for proliferation and differentiation of mammary epithelium during pregnancy...

..Therefore, the purpose of this review is to describe the interactions between MØs and these various cell types and use this knowledge to identify potential functions of MØs in the mammary gland...

..5. To elucidate the role of Chk1 in normal mitosis and genomic instability in breast cancer. ..

..The proximity of two medical schools, Rice University and M.D. Anderson Cancer Center, and the presence of 60,000 professionals make this a unique environment in which to perform medical research ..

..4) To develop a human xenograft model from unfolded Iobules to study early breast cancer progression for comparison with the progression models in the mouse. ..