Disruption of Steroid and Prolactin Receptor Patterning in the Mammary Gland Correlates with a Block in Lobuloalveolar Development (original) (raw)
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1Department of Molecular and Cellular Biology (S.L.G., T.N.S., E.B.K., J.P.L., J.M.R.), Houston, Texas 77030
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1Department of Molecular and Cellular Biology (S.L.G., T.N.S., E.B.K., J.P.L., J.M.R.), Houston, Texas 77030
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1Department of Molecular and Cellular Biology (S.L.G., T.N.S., E.B.K., J.P.L., J.M.R.), Houston, Texas 77030
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3Molecular and Cellular Endocrinology Section (R.C.H., B.K.V.), Bethesda, Maryland 20892
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3Molecular and Cellular Endocrinology Section (R.C.H., B.K.V.), Bethesda, Maryland 20892
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1Department of Molecular and Cellular Biology (S.L.G., T.N.S., E.B.K., J.P.L., J.M.R.), Houston, Texas 77030
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4Center for Cancer Research, National Cancer Institute, National Institutes of Health, and Laboratory of Genetics and Physiology (K.M., L.H.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
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4Center for Cancer Research, National Cancer Institute, National Institutes of Health, and Laboratory of Genetics and Physiology (K.M., L.H.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
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5Cancer Research Program (C.J.O.), Garvan Institute of Medical Research, Darlinghurst, Australia
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2Breast Center (A.V.L.), Department of Medicine, Baylor College of Medicine, Houston, Texas 77030
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Accepted:
16 September 2002
Published:
01 December 2002
Cite
Sandra L. Grimm, Tiffany N. Seagroves, Elena B. Kabotyanski, Russell C. Hovey, Barbara K. Vonderhaar, John P. Lydon, Keiko Miyoshi, Lothar Hennighausen, Christopher J. Ormandy, Adrian V. Lee, Malinda A. Stull, Teresa L. Wood, Jeffrey M. Rosen, Disruption of Steroid and Prolactin Receptor Patterning in the Mammary Gland Correlates with a Block in Lobuloalveolar Development, Molecular Endocrinology, Volume 16, Issue 12, 1 December 2002, Pages 2675–2691, https://doi.org/10.1210/me.2002-0239
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Abstract
Targeted deletion of the bZIP transcription factor, CCAAT/enhancer binding protein-β (C/EBPβ), was shown previously to result in aberrant ductal morphogenesis and decreased lobuloalveolar development, accompanied by an altered pattern of progesterone receptor (PR) expression. Here, similar changes in the level and pattern of prolactin receptor (PrlR) expression were observed while screening for differentially expressed genes in C/EBPβnull mice. PR patterning was also altered in PrlRnull mice, as well as in mammary tissue transplants from both PrlRnull and signal transducer and activator of transcription (Stat) 5a/b-deficient mice, with concomitant defects in hormone-induced proliferation. Down-regulation of PR and activation of Stat5 phosphorylation were seen after estrogen and progesterone treatment in both C/EBPβnull and wild-type mice, indicating that these signaling pathways were functional, despite the failure of steroid hormones to induce proliferation. IGF binding protein-5, IGF-II, and insulin receptor substrate-1 all displayed altered patterns and levels of expression in C/EBPβnull mice, suggestive of a change in the IGF signaling axis. In addition, small proline-rich protein (SPRR2A), a marker of epidermal differentiation, and keratin 6 were misexpressed in the mammary epithelium of C/EBPβnull mice. Together, these data suggest that C/EBPβ 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.
Copyright © 2002 by The Endocrine Society
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