Transforming growth factor beta receptor II gene microsatellite instability in epithelial cancer

B. SUMMARY TRANSFORMING GROWTH FACTOR BETA RECEPTOR II GENE (TGFp-RH) MICROSATELLITE INSTABILITY IN EPITHELIAL CANCER Sefa KIZILDA? Key Words Colorectal cancer, Bilateral Breast cancer, TGFP-RIL MIN Transforming growth factor beta (TGFP) is a potent inhibitor of epithelial cell growth. TGFP actions are mediated by binding to heteromeric complexes of transforming growth factor beta receptor type I (TGFP-RI) and transforming growth factor beta receptor type II (TGFf3-RH). Frameshift mutations of the poliadenine repeat region p(A)i0, in the TGFJÎ-RII gene, were shown to exist in gastric and colon cancer associated with microsattelite instability (MUM). These mutations result in truncated proteins with abolished serin threonine kinase activity. Cells gain resistance to TGFP actions and escape from TGFP mediated growth control, contributing to carcinogenesis. Forty-one epithelial cancer specimens (15 colorectal cancer and 26 bilateral breast cancer) were analysed for mutations of simple repeated sequences in the TGFp-RII. After DNA isolation, the poliadenin region in the TGFP-RII gene was amplified by PCR, using specific primers. The amplification products were run on poliacrilamide gels (with 8M urea) and visualised by silver staining. P(A)io mutations were not detected in any of the colorectal cancer samples and only 1 out of the 26 bilateral breast cancer samples showed allelic shifts representing MTN (%3.84). n