Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells.

Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells. Research Abstract Details 

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Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells. Abstract Text:

Terence M Williams,Federica Sotgia,Hyangkyu Lee,Ghada Hassan,Dolores Di Vizio,Gloria Bonuccelli,Franco Capozza,Isabelle Mercier,Hallgeir Rui,Richard G Pestell,Michael P Lisanti,

Here, we investigate the role of caveolin-1 (Cav-1) in breast cancer onset and progression, with a focus on epithelial-stromal interactions, ie, the tumor microenvironment. Cav-1 is highly expressed in adipocytes and is abundant in mammary fat pads (stroma), but it remains unknown whether loss of Cav-1 within mammary stromal cells affects the differentiated state of mammary epithelia via paracrine signaling. To address this issue, we characterized the development of the mammary ductal system in Cav-1-/- mice and performed a series of mammary transplant studies, using both wild-type and Cav-1-/- mammary fat pads. Cav-1-/- mammary epithelia were hyperproliferative in vivo, with dramatic increases in terminal end bud area and mammary ductal thickness as well as increases in bromodeoxyuridine incorporation, extracellular signal-regulated kinase-1/2 hyperactivation, and up-regulation of STAT5a and cyclin D1. Consistent with these findings, loss of Cav-1 dramatically exacerbated mammary lobulo-alveolar hyperplasia in cyclin D1 Tg mice, whereas overexpression of Cav-1 caused reversion of this phenotype. Most importantly, Cav-1-/- mammary stromal cells (fat pads) promoted the growth of both normal mammary ductal epithelia and mammary tumor cells. Thus, Cav-1 expression in both epithelial and stromal cells provides a protective effect against mammary hyperplasia as well as mammary tumorigenesis.

Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells. Publishing Authors By Initials

TM Williams,F Sotgia,H Lee,G Hassan,D Di Vizio,G Bonuccelli,F Capozza,I Mercier,H Rui,RG Pestell,MP Lisanti,

For similar cells: connective tissue cells: stromal cells research abstracts see: cells: connective tissue cells: stromal cells research

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Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The American journal of pathology

VOLUME: 169

Page Numbers: 1784-801

Journal Abbreviation: Am. J. Pathol.

ISSN: 0002-9440

DAY: 3

MONTH: Nov

YEAR: 2006

Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells. Information

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LANGUAGE: eng

NlmUniqueID: 370502

Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells. Keywords Mesh Terms:

KEYWORDS: Stromal Cells

MESH TERMS: cytology

Chemical & Substance for Abstract: Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells. Information

Substance Name: Mitogen-Activated Protein Kinase 3

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells.

AFFILIATION: Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01CA98779

ACRONYM: CA

MEDLINETA: Am J Pathol

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