help button home button Am J Pathol ASIP WHAT IS IT?
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
A more recent version of this article appeared on February 1, 2008

Published online before print January 17, 2008
This Article
Right arrow Full Text (Rapid PDF)
Right arrow All Versions of this Article:
ajpath.2008.070696v1
172/2/345    most recent
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 Google Scholar
Google Scholar
Right arrow Articles by Bianco, C.
Right arrow Articles by Salomon, D. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bianco, C.
Right arrow Articles by Salomon, D. S.
Copyright © 2008 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2008.070696

Accepted for publication November 7, 2007.

Article

Regulation of Cripto-1 Signaling and Biological Activity by Caveolin-1 in Mammary Epithelial Cells

Caterina Bianco*, Luigi Strizzi*, Mario Mancino*, Kazuhide Watanabe*, Monica Gonzales*, Shin Hamada*, Ahmed Raafat{dagger}, Lawson Sahlah{dagger}, Cindy Chang{ddagger}, Federica Sotgia{sect}, Nicola Normanno||, Michael Lisanti{sect}, and David S. Salomon*@

From the Tumor Growth Factor* and Oncogenetics{dagger} Sections, Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; the New Jersey Dental School,{ddagger} University of Medicine and Dentistry of New Jersey, Newark, New Jersey; the Department of Cancer Biology,{sect} Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; and the Cell Biology and Preclinical Models Unit,|| ITN-Fondazione Pascale, Naples, Italy

@ To whom correspondence should be addressed. E-mail: salomond{at}mail.nih.gov.


  Abstract

Human and mouse Cripto-1 (CR-1/Cr-1) proteins play an important role in mammary gland development and tumorigenesis. In this study, we examined the relationship between Cripto-1 and caveolin-1 (Cav-1), a membrane protein that acts as a tumor suppressor in the mammary gland. Cripto-1 was found to interact with Cav-1 in COS7 cells and mammary epithelial cells. Using EpH4 mouse mammary epithelial cells expressing Cr-1 (EpH4 Cr-1) or Cr-1 and Cav-1 (EpH4 Cr-1/Cav-1), we demonstrate that Cav-1 expression markedly reduced the ability of Cr-1 to enhance migration, invasion, and formation of branching structures in EpH4 Cr-1/Cav-1 cells as compared to EpH4 Cr-1 cells. Furthermore, coexpression of Cav-1 together with Cr-1 in EpH4 Cr-1/Cav-1 cells inhibited Cr-1-mediated activation of c-src and mitogen-activated protein kinase signaling pathways. Conversely, primary mammary epithelial cells isolated from Cav-1 null-/-/mouse mammary tumor virus-CR-1 transgenic animals showed enhanced motility and activation of mitogen-activated protein kinase and c-src as compared to Cav-1+/-/CR-1 mammary cells. Finally, mammary tumors derived from mouse mammary tumor virus-CR-1 mice showed a dramatic reduction of Cav-1 expression as compared to mammary tissue from normal FVB/N mice, suggesting that in vivo Cav-1 is down-regulated during the process of CR-1-mediated mammary tumorigenesis.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2008 by the American Society for Investigative Pathology.