The Journal of Experimental Medicine
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Published 3 November 2003. doi:10.1084/jem.20030580
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© 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


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