The Journal of Experimental Medicine
Randox
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 3 November 2003. doi:10.1084/jem.20030580
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mañes, S.
Right arrow Articles by Martínez-A., C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mañes, S.
Right arrow Articles by Martínez-A., C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2003/11/1381 $5.00
The Journal of Experimental Medicine, Volume 198, Number 9, 1381-1389

CCR5 Expression Influences the Progression of Human Breast Cancer in a p53-dependent Manner

Santos Mañes1, Emilia Mira1, Ramón Colomer2, Sagrario Montero2, Luis M. Real4, Concepción Gómez-Moutón1, Sonia Jiménez-Baranda1, Alfredo Garzón3, Rosa Ana Lacalle1, Keith Harshman1, Agustín Ruíz4 and Carlos Martínez-A.1

1 Department of Immunology and Oncology, Centro Nacional de Biotecnología, Universidad Autonoma de Madrid, E-28049 Madrid, Spain
2 Medical Oncology, Hospital Universitario 12 de Octubre, E-28041 Madrid, Spain
3 Pathology Department, Hospital Universitario 12 de Octubre, E-28041 Madrid, Spain
4 Department of Structural Genomics, Neocodex, E-41020 Seville, Spain

Address correspondence to Santos Mañes, Department of Immunology and Oncology, Centro Nacional de Biotecnología, Campus de Cantoblanco, Universidad Autonoma de Madrid, E-28049 Madrid, Spain. Phone: 34-91-585-4660; Fax: 34-91-372-0493; e-mail: smanes{at}cnb.uam.es

Chemokines are implicated in tumor pathogenesis, although it is unclear whether they affect human cancer progression positively or negatively. We found that activation of the chemokine receptor CCR5 regulates p53 transcriptional activity in breast cancer cells through pertussis toxin–, JAK2-, and p38 mitogen–activated protein kinase–dependent mechanisms. CCR5 blockade significantly enhanced proliferation of xenografts from tumor cells bearing wild-type p53, but did not affect proliferation of tumor xenografts bearing a p53 mutation. In parallel, data obtained in a primary breast cancer clinical series showed that disease-free survival was shorter in individuals bearing the CCR5{Delta}32 allele than in CCR5 wild-type patients, but only for those whose tumors expressed wild-type p53. These findings suggest that CCR5 activity influences human breast cancer progression in a p53-dependent manner.

Key Words: chemokine receptor • breast cancer • p53 • CCR5 polymorphism • p38


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS