Prolactin Negatively Regulates Caveolin-1 Gene Expression in the Mammary Gland during Lactation, via a Ras-dependent Mechanism

David S. Park, Hyangkyu Lee, Claudia Riedel, James Hulit, Philipp E. Scherer, Richard G. Pestell, Michael P. Lisanti

Research output: Contribution to journalArticle

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Abstract

Caveolin-1 is a 22-kDa integral membrane protein that has been suggested to function as a negative regulator of mitogen-stimulated proliferation in a variety of cell types, including mammary epithelial cells. Because much of our insight into caveolin-1 function has come from the study of human breast tumor-derived cell lines in culture, the normal physiological regulators of caveolin-1 expression in the mammary gland remain unknown. Here, we examine caveolin-1 expression in mice at different stages of mammary gland development. We show that caveolinol-1 expression is significantly down-regulated during late pregnancy and lactation. Upon weaning, mammary gland expression of caveolin-1 rapidly returns to non-pregnant "steady-state" levels. Injection of virgin mice with a battery of hormones normally up-regulated during lactation demonstrates that prolactin is the main mediator of caveolin-1 down-regulation. Virtually identical results were obtained with human mammary epithelial cells (hTERT-HME1) in culture. In addition, we demonstrate that prolactin-mediated down-regulation of caveolin-1 expression occurs at the level of transcriptional control and via a Ras-dependent mechanism. Interestingly, in the mammary gland, both mammary epithelial cells and the surrounding mammary adipocytes show prolactin-mediated down-regulation of caveolin-1. This hormone-dependent regulation of caveolin-1 expression is specific to the mammary fat pad. Finally, we employed HC11 cells, a well-established model of mammary epithelial cell differentiation, to study the possible functional effects of caveolin-1 expression. In the presence of lactogenic hormones, recombinant expression of caveolin-1 in HC11 cells dramatically suppresses the induction of the promoter activity and the synthesis of β-casein, an established reporter of lactogenic differentiation and milk production. These findings may explain why caveolin-1 levels are normally down-regulated during lactation. This report is the first demonstration that caveolin-1 levels are down-regulated during a normal physiological event in vivo, i.e. lactation, because previous reports have only documented that down-regulation of caveolin-1 occurs during cell transformation and tumorigenesis.

Original languageEnglish
Pages (from-to)48389-48397
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number51
DOIs
Publication statusPublished - 2001 Dec 21

Fingerprint

Caveolin 1
Human Mammary Glands
Lactation
Gene expression
Prolactin
Gene Expression
Breast
Down-Regulation
Epithelial Cells
Hormones
Caseins
Weaning
Tumor Cell Line
Mitogens
Cell culture
Adipocytes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Park, David S. ; Lee, Hyangkyu ; Riedel, Claudia ; Hulit, James ; Scherer, Philipp E. ; Pestell, Richard G. ; Lisanti, Michael P. / Prolactin Negatively Regulates Caveolin-1 Gene Expression in the Mammary Gland during Lactation, via a Ras-dependent Mechanism. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 51. pp. 48389-48397.
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Prolactin Negatively Regulates Caveolin-1 Gene Expression in the Mammary Gland during Lactation, via a Ras-dependent Mechanism. / Park, David S.; Lee, Hyangkyu; Riedel, Claudia; Hulit, James; Scherer, Philipp E.; Pestell, Richard G.; Lisanti, Michael P.

In: Journal of Biological Chemistry, Vol. 276, No. 51, 21.12.2001, p. 48389-48397.

Research output: Contribution to journalArticle

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T1 - Prolactin Negatively Regulates Caveolin-1 Gene Expression in the Mammary Gland during Lactation, via a Ras-dependent Mechanism

AU - Park, David S.

AU - Lee, Hyangkyu

AU - Riedel, Claudia

AU - Hulit, James

AU - Scherer, Philipp E.

AU - Pestell, Richard G.

AU - Lisanti, Michael P.

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