Microsatellite mutation of the polyadenine tract (10 adenine repeat) within the TbetaR-II [transforming growth factor-beta (TGF-beta) receptor type II] coding region have been found in a variety of human cancers, particularly in association with microsatellite instability (MSI). Since breast cancers have been reported to carry MSI, although its frequencies were quite variable, we examined whether microsatellite mutation of the polyadenine tract occurs in the human breast cancer MDA-MB-231 cell line. TbetaR-II expression in MDA-MB-231 was found to be low on our Northern and Western analyses. Sequencing analysis for the polyadenine tract of TbetaR-II cDNA obtained from MDA-MB-231 cells indicated heterozygous deletion of one adenine base. Subsequently, sensitivity to TGF-beta induced growth-inhibitory effects of control and TbetaR-II transfected MDA-MB-231 cells was compared. The sensitivity of TbetaR-II transfectants to exogenous as well as endogenous TGF-beta1 was increased distinctly compared with control transfectant. These results suggest that heterozygous deletion of one adenine base within the polyadenine tract in MDA-MB-231 cells might lead to reduced TbetaR-II expression and sensitivity to TGF-beta.

Related Articles