Adiponectin mediates an antiproliferative response in human MDA-MB 231 breast cancer cells.
Numerous epidemiological studies have documented that obesity is a risk factor for breast cancer especially in post-menopausal women. However, the molecular basis of this association is not well known. In contrast to leptin, plasma levels of adiponectin, another major adipokine, are decreased in obese subjects. Therefore, we and others hypothesized that adiponectin may be a paracrine factor negatively controlling mammary tumor development. We recently demonstrated growth inhibition of the estrogen-sensitive breast cancer MCF-7 cell line by adiponectin. The purpose of the present study was to determine whether this anti-proliferative effect of adiponectin also applies to the MDA-MB 231 estrogen-insensitive breast epithelial cancer cell line. Our results demonstrate that i) the adiponectin-specific receptors AdipoR1 and R2 are expressed in these cells, and ii) the subphysiological concentrations of recombinant adiponectin inhibit MDA-MB 231 cell growth and concomitantly enhance the expression of Bax and p53, two pro-apoptotic genes. Moreover, the invalidation of AdipoR1 and R2 mRNA experiments demonstrated that the anti-proliferative and pro-apoptotic effects of adiponectin were partially mediated via AdipoR1 and R2. We describe, for the first time, that AdipoR mRNA expression was down-regulated by adiponectin and leptin in MDA-MB 231 cells. Taken altogether, these results strongly suggest that the two adipokines should be considered as i) additional factors of breast cancer risk, and ii) may therefore be potential targets in breast cancer therapy.
Dos Santos
Esther
E
Université Versailles-St Quentin, Service de Biochimie et Biologie Moléculaire, UPRES-EA 2493, Faculté de Médecine Paris-Ile de France Ouest, Centre Hospitalier de Poissy, 78303 Poissy Cedex, France.
Benaitreau
Delphine
D
Dieudonne
Marie-Noëlle
MN
Leneveu
Marie-Christine
MC
Serazin
Valérie
V
Giudicelli
Yves
Y
Pecquery
René
R
D052242:Adiponectin / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D005260:Female; D016158:Genes, p53; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D054419:Receptors, Adiponectin / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
D052242:Adiponectin; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D019938:Cyclin D1