Obesity is characterized by an excess of adipose tissue, due to adipocyte
hypertrophy and
hyperplasia. Adipose tissue is an endocrine organ producing many bioactive molecules, called
adipokines. During
obesity, dysfunctional adipocytes alter
adipokine secretion, contributing to pathophysiology of
obesity-associated diseases, including
metabolic syndrome, type 2-diabetes,
cardiovascular diseases and many types of
malignancies. Circulating
adiponectin levels are inversely correlated with BMI, thus
adiponectin concentrations are lower in obese than normal-weight subjects. Many clinical investigations highlight that low
adiponectin levels represent a serious risk factor in breast
carcinogenesis, and are associated with the development of more aggressive phenotype. A large-scale meta-analysis suggests that BMI was positively associated with
breast cancer mortality in women with ERα-positive disease, regardless menopausal status. This suggests the importance of
estrogen signaling contribution in breast
tumorigenesis of obese patients. It has been largely demonstrated that
adiponectin exerts a protective role in ERα-negative cells, promoting anti-proliferative and pro-apoptotic effects, while controversial data have been reported in ERα-positive cells. Indeed, emerging data provide evidences that
adiponectin in obese patients behave as
growth factor in ERα-positive
breast cancer cells. This addresses how ERα signaling interference may enhance the potential inhibitory threshold of
adiponectin in ERα-positive cells. Thus, we may reasonably speculate that the relatively low
adiponectin concentrations could be still not adequate to elicit, in ERα-positive
breast cancer cells, the same inhibitory effects observed in ERα-negative cells. In the present review we will focus on the molecular mechanisms through which
adiponectin affects
breast cancer cell behavior in relationship to ERα expression.