Insulin-like growth factor (IGF)-system mRNA quantities in normal and tumor breast tissue of women with sporadic and familial breast cancer risk

The insulin-like growth factor (IGF)-system plays a role in breast cancer susceptibility as well as in growth and progression of breast carcinomas. So far, findings have been based on serum IGF-I levels and semi-quantitative assessment of IGF-system expression levels in model systems and human tissue. Quantitative data on mRNA expression in different types of human breast tissue are lacking. Breast tissue samples (n = 83) were available from 72 women. Messenger RNA expression of IGF-I, IGF-II, and their receptors (IGF-1R and IGF-2R) was assessed by real-time RT-PCR. We found a large variation in mRNA levels. Expression of each gene was significantly higher in normal tissue than in tumor tissue ( median for normal and tumor tissue, respectively ( arbitrary units); IGF-I: 25.2 and 1.4; IGF-II: 5.9 and 0.6; IGF-1R: 0.18 and 0.07; IGF-2R: 1.8 and 0.9; p< 0.0001, Mann - Whitney test). Interestingly, in tumor tissue from patients with a strong family history of breast cancer, expression of both receptors was higher than in sporadic patients ( IGF-1R: 0.13 and 0.05, p=0.04; IGF- 2R: 1.1 and 0.8, p = 0.04). For cancer-free controls, expression of IGF-II and IGF- 2R in normal breast tissue was also higher in women with a family history of breast cancer than in women without such a family history ( IGF- II: 7.2 and 1.5, p = 0.02; IGF- 2R: 2.6 and 1.5, p = 0.09). Our study quantitatively shows that mRNA expression levels of IGF- system components in the breast are generally higher in normal tissue compared with tumor tissue, and higher in tissue from women with a family history of breast cancer. A basis has therefore been created for studies aimed at understanding IGF as a breast cancer risk factor, the relationship between IGF- systems in serum and tissues, and effects of lifestyle factors on the IGF- system.