help button home button Am J Pathol International Conference on Pathology of Chest Diseases
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Williams, T. M.
Right arrow Articles by Lisanti, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Williams, T. M.
Right arrow Articles by Lisanti, M. P.
(American Journal of Pathology. 2006;169:1784-1801.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060590

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

Terence M. Williams*, Federica Sotgia*{dagger}, Hyangkyu Lee*, Ghada Hassan*, Dolores Di Vizio{ddagger}, Gloria Bonuccelli*, Franco Capozza*, Isabelle Mercier*, Hallgeir Rui*, Richard G. Pestell* and Michael P. Lisanti*{dagger}

From the Department of Cancer Biology,* Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; the John F. Enders Research Laboratories,{ddagger} Children’s Hospital, Harvard Medical School, Boston, Massachusetts; and the Muscular and Neurodegenerative Disease Unit,{dagger} University of Genova and G. Gaslini Pediatric Institute, Genova, Italy

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.





This article has been cited by other articles:


Home page
Endocr Relat CancerHome page
S.-H. Tan and M. T Nevalainen
Signal transducer and activator of transcription 5A/B in prostate and breast cancers
Endocr. Relat. Cancer, June 1, 2008; 15(2): 367 - 390.
[Abstract] [Full Text] [PDF]


Home page
J. Histochem. Cytochem.Home page
N. Odajima, T. Betsuyaku, Y. Nasuhara, and M. Nishimura
Loss of Caveolin-1 in Bronchiolization in Lung Fibrosis
J. Histochem. Cytochem., September 1, 2007; 55(9): 899 - 909.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Society for Investigative Pathology.