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Developmental and hormonal regulation of mammary gland gene expression and breast cancer
The research objectives of my laboratory are to elucidate the mechanisms regulating the normal development
of the mammary gland, including the hormonal control of milk protein gene expression, and to determine how these regulatory
mechanisms have deviated in breast cancer.
Critical periods of postnatal development in the mouse mammary gland include ductal proliferation and branching that
occur during sexual maturity, lobuloalveolar proliferation that occurs during pregnancy, terminal differentiation that results
in lactation, and involution characterized by increased apoptosis and extensive tissue remodeling. Studies of the role of
systemic hormones (viz., prolactin, glucocorticoids, estrogens and progestins) and local growth factors, including members of
the Wnt, Fgf, and IGF families, on each of these processes are under way. The role of specific transcription factors and their
dominant-negative isoforms, including members of the C/EBP, Stat and NF I families, are also being examined using transgenic
and knockout mouse models. Gene arrays and subtractive hybridization techniques are employed to identify downstream targets
of these transcription factors. Postnatal mammary gland development is being studied in knockout mice displaying late
embryonic or neonatal mortality by transplantation of mammary epithelium into the cleared mammary gland fat pad of syngeneic
recipients. Genetically engineered mice coupled with FACS analysis and transplantation into the cleared mammary fat pad has
also been employed as model system in which to isolate and characterize functional mammary progenitors and stem cells.
Finally, transgenic and knockout mouse models are being used to elucidate changes in normal mammary gland stem cells and
progenitors and signal transduction pathways that are involved in the progression from the normal mammary gland to
preneoplasias, as well as the role of mutant p53 and Chk1 in genomic instability and the development of aneuploidy.
Selected Publications
Ginger MR, Gonzalez-Rimbau MF, Gay JP, Rosen JM (2001) Persistent changes in gene expression
induced by estrogen and progesterone in the rat mammary gland. Molecular Endocrinology 15:1993-2009.
Kingsley-Kallesen M, Mukhopadhyay SS, Wyszomierski SL, Schanler S, Schutz G, Rosen JM (2002) The
mineralocorticoid receptor may compensate for the loss of the glucocorticoid receptor at specific stages of mammary
gland development. Molecular Endocrinology 16:2008-2018.
Welm BE, Tepera SB, Venezia T, Graubert TA, Rosen JM, Goodell MA (2002) Sca-1pos cells in the mouse
mammary gland represent an enriched progenitor cell population. Developmental Biology 245:42-56.
Welm BE, Freeman KW, Chen M, Contreras A, Spencer DM, Rosen JM (2002) Inducible dimerization of FGFR1:
development of a mouse model to analyze progressive transformation of the mammary gland. Journal of Cell Biology
157:703-714.
Grimm SL, Seagroves TN, Kabotyanski EB, Hovey RC, Vonderhaar BK, Lydon JP, Miyoshi K, Hennighausen L,
Ormandy CJ, Lee AV, Stull MA, Wood TL, Rosen JM (2002) Disruption of steroid and prolactin receptor patterning
in the mammary gland correlates with a block in lobuloalveolar development. Molecular Endocrinology
16:2675-2691.
Tepera SB, McCrea PD, Rosen JM (2003) A β-catenin survival signal is required for normal lobular
development in the mammary gland. Journal of Cell Science 116:1137-1149.
Kabotyanski EB, Rosen JM (2003) Signal transduction pathways regulated by prolactin and Src result in
different conformations of activated Stat5b. Journal of Biological Chemistry 278:17218-17227.
Chakravarty G, Hadsell D, Buitrago W, Settleman J, Rosen JM (2003) p190-B RhoGAP regulates mammary
ductal morphogenesis. Molecular Endocrinology 17:1054-1065.
Contact Information
- Jeffrey M. Rosen, Ph.D.
- Department of Molecular and Cellular Biology
- Baylor College of Medicine
- One Baylor Plaza M638
- Houston, Texas 77030, U.S.A.
Lab Website
- Tel: (713) 798-6210
- Fax: (713) 798-8012
- E-mail: jrosen@bcm.tmc.edu
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