PRL activates the cyclin D1 promoter via the Jak2/Stat pathway

Molecular Endocrinology
Jennifer L BrockmanL A Schuler

Abstract

PRL promotes cell growth and differentiation in the mammary gland, which has implications for breast cancer as well as normal development. Our data demonstrate that PRL significantly increases proliferation of mammary carcinoma cells. PRL also increases cyclin D1 levels 2-fold, which can be inhibited by actinomycin D, suggesting that transcriptional increases in cyclin D1 are important. Using a defined Chinese hamster ovary cell model system, we demonstrate that the activity of a cyclin D1 promoter-luciferase construct increases after PRL treatment. Furthermore, this increase in promoter activity is predominantly mediated by the Jak2/Stat5 signaling pathway. The cyclin D1 promoter contains two consensus sequences for PRL-induced Stat binding (GAS sites). Disruption of Stat binding to the distal GAS site destroys PRL-induced promoter activity, whereas disruption of the proximal site has no effect. We have shown by EMSA that PRL induces Stat5a and 5b to bind to the distal GAS site, and immunoprecipitation and subsequent Western analysis of nuclear extracts from PRL-treated cells indicate that Stat5a and 5b can interact as a heterodimer in this system. These data suggest that cyclin D1 may be a target gene for PRL in normal lobulo...Continue Reading

Citations

May 12, 2005·Molecular and Cellular Endocrinology·Jennifer L Brockman, Linda A Schuler
Jul 25, 2003·Oncogene·Teresa A Rose-HellekantLinda A Schuler
Dec 4, 2003·Molecular and Cellular Biology·Sophie MagnéIsabelle Dusanter-Fourt
Feb 1, 2011·Breast Cancer Research : BCR·Lisa M ArendtLinda A Schuler
Feb 18, 2003·Endocrine Reviews·Charles V ClevengerLinda A Schuler
Aug 21, 2004·Molecular Endocrinology·Jennifer H GutzmanLinda A Schuler
Jul 2, 2011·Molecular Endocrinology·Jing TaoMaria Diakonova
Mar 20, 2010·Journal of Molecular Endocrinology·Feng FangCharles V Clevenger
Feb 8, 2008·BMC Biotechnology·Feng FangCharles V Clevenger
Jan 30, 2008·Journal of Mammary Gland Biology and Neoplasia·Kay-Uwe Wagner, Hallgeir Rui
Dec 19, 2006·FEBS Letters·Andriana D Papaconstantinou, Elizabeth G Snyderwine
Oct 29, 2004·The American Journal of Pathology·Charles V Clevenger
Feb 13, 2010·Trends in Endocrinology and Metabolism : TEM·Nadine BinartJustine Bouilly
Jun 19, 2009·Trends in Endocrinology and Metabolism : TEM·Charles V ClevengerJiamao Zheng
Jun 23, 2015·Cancer Letters·Tomohiro YonezawaAmeae M Walker
Jun 16, 2004·Molecular and Cellular Endocrinology·Silvana BordinAntonio C Boschero
Oct 8, 2005·Seminars in Hematology·Ayalew Tefferi, Jerry L Spivak
May 27, 2014·PloS One·Jimena FerrarisDaniel Pisera
Oct 31, 2006·Molecular and Cellular Endocrinology·Massimiliano MottaMario Baratta
Mar 21, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Shelley S TworogerSusan E Hankinson

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