Molecular significance of excess body weight in postmenopausal breast cancer patients, in relation to expression of insulin-like growth factor I receptor and insulin-like growth factor II genes

A number of epidemiological and clinical studies have revealed that excess body weight increases the risk of postmenopausal breast cancer and also adv ersely affects subsequent malignant progression. To elucidate the molecular mechanisms underlying these observations, we examined mRNA expression of v arious genes in normal (non-cancerous) mammary gland and cancer tissue of J apanese patients with primary breast cancer, in association with their body mass index (BR II). On the basis of analysis of 106 breast cancer patients , we found that mRNA expression of insulin-like growth factor I receptor (I GF-IR) and insulin-like growth fatter II (IGF-ZI) in the normal mammary gla nd showed a significant and positive association with increased BMI among p ostmenopausal patients. Furthermore, the positive association of increased BMI with IGF-IR mRNA expression was also found in postmenopausal breast can cer tissue, while this association was not observed among premenopausal pat ients. In addition, increased mRNA expression of cyclin D1 and bcl-2 was ob served in association with increased mRNA levels of IGF-IR among the patien ts regardless of menopausal status. These findings suggest that the molecul ar consequence of the increased BR-II is the increased expression of IGF-II and IGF-IR, resulting in development of postmenopausal breast cancer and i ts progression mediated through modulation of the cell cycle and apoptosis.