CCR5 expression influences the progression of human breast cancer in a p53-dependent manner.
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 CCR5Delta32 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.
Mañes
Santos
S
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Universidad Autonoma de Madrid, E-28049 Madrid, Spain. smanes@cnb.uam.es
Mira
Emilia
E
Colomer
Ramón
R
Montero
Sagrario
S
Real
Luis M
LM
Gómez-Moutón
Concepción
C
Jiménez-Baranda
Sonia
S
Garzón
Alfredo
A
Lacalle
Rosa Ana
RA
Harshman
Keith
K
Ruíz
Agustín
A
Martínez-A
Carlos
C
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D018450:Disease Progression; D006801:Humans; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019713:Receptors, CCR5; D016159:Tumor Suppressor Protein p53