Co-expression of genes of the insulin- and estrogen signaling system and correlation with clinical parameters in breast cancer patients

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Obesity is thought to increase breast cancer risk both through high activity of estrogen metabolizing enzymes and by associated high insulin and glucose serum levels directly impacting on proliferation and apoptosis of breast cancer cells. In the present study, we investigated co-expression of genes of the insulin/ IGF axis and the estrogen signaling system in correlation to clinical parameters in collected breast cancer specimen. Breast cancer tissue and fasting serum was collected from 26 female patients. After microdissection of the frozen samples, RNA was isolated and expression of genes of the estrogen- and insulin/IGF signaling was measured by real time RT PCR. Fasting insulin, glucose and C-peptide as well as estradiol serum level were analysed by ELISA. Insulin resistance was calculated by the HOMA method. Postmenopausal women older than 70 years showed significant higher expression of estrogen receptor (ER) α as well as steroid sulfatase (STS) and were more likely insulin resistant than premenopausal women younger than 50 years. A strong significant association between vascular/ lymphovascular invasion (L1, V1) and BMI as well as insulin resistance could be identified. Both, ERα and STS expression were significantly associated with expression of insulin receptor, IGFR1 and IGFBP4 but not IGFR2. Higher expression of IGFR1 was associated with a better histological grading, whereas higher expression of IGFR2 correlated with lymph node negativity. In conclusion, the observed co-expression of components of the insulin/IGF signaling with ERα and steroid sulfatase supports the hypothesis that a close cross talk between both pathways is present in breast cancer cells. The observed correlation of insulin resistance with vascular invasion encourages further studies on larger case numbers to further examine the relevance of this association in the clinical situation.