Adiponectin differentially affects gene expression in human mammary epithelial and breast cancer cells

Abstract

Serum levels of adiponectin are inversely associated with breast cancer risk. In this study, its effect on growth and gene expression of MCF-7 breast cancer cells and MCF-10A human mammary epithelial cells was compared. The antiproliferative effect of adiponectin on MCF-10A cells was more pronounced and was accompanied by elevated transcript levels of caspase 1, ERb2, ERb5, TR2 and USP2. Our data suggest that upregulation of genes with known growth inhibitory or apoptotic functions in mammary epithelial cells might contribute to the protective action of this adipocytokine.

Quantification of Steroid Receptors Gene Expression in Breast Cancer Patients: Possible Correlation with Serum Level of Adipocytokines

“…Treeck et al postulated that there is a crosstalk between adiponectin and ER signaling. In their study In MCF-10A cells, adiponectin triggered a significant increase of ERβ2 and ERβ5 mRNA levels [24]. ERβ is the dominant estrogen receptor in normal breast tissue [10], but its expression declines during tumorigenesis, but at the other hand expression of ERα that can exert mitogenic effects-increases during tumorgenesis [29].…”

“…It is notable that these three adipocytokins can stimulate estrogen biosynthesis by the induction of aromatase activity [16]. As ERα is known to mediate tu-mour-promoting effects of 17-b estradiol [18], data suggest that adiponectin-triggered increase of ERβ isoform expression might be one important molecular mechanism underlying the protective effects of this adipocytokine [24]. Also the relation between obesity and adipocytokins well studied but there is no information about the possible effect of steroid hormones on secretion of these adipocytokines in obese and none obese breast cancer subjects.…”

Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies

“…However, we observed that adiponectin downregulated ERa mRNA and tended to downregulate aromatase mRNA. Recently, Treeck et al (2008) have showed that adiponectin increased the mRNA expression of ERb5 in MCF-7 cells, a protein known to negatively interfere with the transcriptional activity of ERa. These results suggest a potential anti-proliferative role of adiponectin in breast cancer, mediated by the decreased in situ estradiol production and decreased sensitivity of cancer cells.…”

Adiponectin Can Affect ER Signaling in Obese Breast Cancer Patients

“…It is tempting to speculate that the E2-triggered down-regulation of AdipoR1 may be a signaling crosstalk directly affecting breast cancer risk (16 Treeck and his colleagues postulated that there is a cross talk between adiponectin and ER signaling. In their study on MCF-10A cells, adiponectin triggered a significant increase of ERβ2 and ERβ5 mRNA levels [17]. The antimitogeneic activites of ERβ attributed to ERβ2 (also known as ERβcx) [9].…”

“…While excess adipose tissue in obese subjects increase production of most of adipokines such as leptin, obese subjects have a lower serum level of adiponectin in comparison to their lean counterparts, moreover weigh loss can increase serum level of adiponectin [3,15]. Many in vitro studies revealed the anti-tumoral effects of this adipocytokine such as its anti-angiogenic, pro apoptotic, anti inflammatory and anti prolifrative activities that propose it as a potent tumor suppressor gene [16,17]. Recently it is proposed that there may be a crosstalk between this adipokine and estrogen receptor signaling [11,17], so the aim of this study was to determine the possible connection between serum level of adiponectin and ERα and ERβ gene expression in breast cancer tissues.…”