Evidence for a tumour suppressive function of IGF1-binding proteins in human breast cancer.

UNLABELLED The role of the insulin like growth factor (IGF) system in various human malignancies has been well established. The aim of this study was to determine the levels of mRNA expression of insulin-like growth factor-binding protein (IGFBP)-1, -3 and -7 genes in benign and malignant breast tissue and explore their relationship with various prognostic parameters. MATERIALS AND METHODS Breast cancer tissue (n=127) and normal background tissue (n-33) were prospectively collected and analysed for levels of IGFBP-1, -3 and -7 mRNA using real-time Q-PCR. mRNA levels were then analysed against tumour grade, nodal status, Nottingham prognostic index (NPI)/TNM stage and tumour type. RESULTS For IGFBP-1 and -3, mRNA expression was higher in normal tissue. This was significant for IGFBP-1 when comparing NPI 3 with NPI 1 (p=0.050) and the normal group (p=0.040). With respect to TNM analysis, there was less IGFBP-1 mRNA when comparing TNM 3 with normal (p=0.017), TNM 1 (p=0.047) and TNM 2 (p=0.019) tumours. This was also found when comparing TNM 4 samples with normal tissue (p=0.017), TNM 1 (p=0.046) and TNM 2 (p=0.019). For IGFBP-3 mRNA, there was less mRNA when comparing TNM 3 with TNM 1 (p= 0.017) and TNM 2 (p=0.050), and also less mRNA expression when comparing TNM 4 with TNM 1 (p=0.030). For IGFBP-7 mRNA, both TNM 1 (p=0.0077) and TNM 2 (p=0.015) had significantly more expression than TNM 3 samples. CONCLUSION This study supports the role of IGFBP-1, -3 and -7 as potential tumour suppressor genes in human breast cancer.