期刊
ENDOCRINE-RELATED CANCER
卷 16, 期 4, 页码 1197-1210出版社
BIOSCIENTIFICA LTD
DOI: 10.1677/ERC-09-0043
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资金
- French Ami-Cancer League (Ligue Contre le Cancer du Puy-de-Dome)
- Deutsche Forschungsgemenischaft [BU 1141/3-2]
- French Ministry of Research and Technology
Obesity is a risk factor for breast cancer development. A recent hypothesis suggests that the adipokines, adiponectin and leptin, are involved in breast cancer development. This prompted us to investigate the role of adiponectin and leptin in mammary carcinogenesis. Adiponectin receptors (AdipoR1 and AdipoR2) and leptin receptor (Ob-Rt, representing all the isoforms of Ob-R) proteins were detected by immunohistochemistry in in situ ductal carcinoma, invasive ductal malignancy, and healthy adjacent tissue. In addition, mRNA expression of adiponectin, AdipoR1, AdipoR2, leptin, Ob-Rt, and Ob-RI (the long isoform of Ob-R) was observed in MCF-7 breast cancer cells Interestingly, leptin mRNA expression was 34.7-fold higher than adiponectin mRNA expression in the MCF-7 cell line. Moreover, adiponectin (10 mu g/ml) tended to decrease the mRNA expression of leptin (-36%) and Ob-RI (-28%) and significantly decreased Ob-Rt mRNA level (-26%) In contrast, leptin treatment (1 mu g/ml) significantly decreased AdipoR1 mRNA (-23%). Adiponectin treatment (10 mu g/ml) inhibited the proliferation of MCF-7 cells, whereas leptin (1 mu g/ml) stimulated the growth of cancer cells In addition, adiponectin inhibited leptin-induced cell proliferation (both 1 mu g/ml). Using microarray analysis, we found that adiponectin reduced the mRNA levels of genes involved in cell cycle regulation (mitogen-activated protein kinase 3 and ATM), apoptosis (BAG1, BAG3, and TP53), and potential diagnosis/prognosis markers (ACADS, CYP19A1, DEGS1, and EVL), whereas leptin induced progesterone receptor mRNA expression. In conclusion, the current study indicates an interaction of leptin- and adiponectin-signaling pathways in MCF-7 cancer cells whose proliferation is stimulated by leptin and suppressed by adiponectin Endocrine-Related Cancer (2009) 16 1197-1210
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