Expression of the insulin-like growth factor-I receptor and proapoptotic Bax and Bak proteins in human colorectal cancer

Insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR), despite their well-known roles in cell survival and proliferation, can also weakly enhance apoptosis. To study the relationships between the IGF-IR and Bax as well as Bak, 144 cases of colorectal cancer were examined by immunohistochemistry, using the avidin-biotin-peroxidase method. The results were correlated with selected clinicopathological features of colorectal cancer and with the expression of IGF-IR, Bax, and Bak in normal colon mucosa. In Bax-, Bak-, or IGF-IR-positive cancers, the adjacent colorectal mucosa revealed positive immunostaining for these proteins. In the majority of Bax-, Bak-, or IGF-IR-negative tumors, we observed no staining for these proteins in adjacent mucosa. The strong immunostaining for IGF-IR, Bax, and Bak was noted in 50.8, 55.5, and 493% of tumors, respectively. We observed positive correlations between IGF-IR and Bax (P < 0.002, r = 0.302), between IGF-IR and Bak (P < 0.0001, r = 0.407), and between Bax and Bak (P < 0.0001, r = 0.474). No relationship was noted between IGF-IR expression and tumor grade, stage, or lymph node status. We found negative associations between Bax, Bak, and tumor grade (P < 0.01 and P < 0.003, respectively), but no relationships between Bax and Bak and tumor stage or between Bax and Bak and lymph node status. Our results demonstrate that, in addition to overexpressed IGF-IR, there are relationships between IGF-IR and proapoptotic proteins in colorectal carcinomas that could contribute to increased cell turnover and the progression of colorectal cancer.