Restoration of Transforming Growth Factor-β Type II Receptor Reduces Tumorigenicity in the Human Adrenocortical Carcinoma SW-13 Cell Line

Transforming growth factor-β (TGF-p) is a potent growth suppressor. Acquisition of TGF-β resistance has been reported in many tumors, and has been associated with reduced TGF-p receptor expression. In this study, we examined TGF-β 1, TGF-β type I receptor (TβRI) and TGF-β type II receptor (TβRII) expression in SW-13 adrenocortical carcinoma cells by Northern and Western blot analysis. SW-13 cells did not express TβRII mRNA or protein. We have investigated the role of TβRII in modulating tumorigenic potential using stably transfected SW-13 cells with TβRII expression plasmid. TβRII-positive SW-13 cell growth was inhibited by exogenous human TGF-β1 (hTGF-β1) in a dose-dependent manner. In contrast, SW-13 cells and control clones transfected with empty vector remained hTGF-β1-insensitive. Xenograft examination in athymic nude mice demonstrated that TβRII-positive SW-13 cells reduced tumor-forming activity. Reconstructing the TβRII can lead to reversion of the malignant phenotype of TβRII-negative human adrenocortical carcinoma, which contains SW-13 cells. Reduced TβRII expression may play a critical role in determining the malignant phenotype of human adrenocortical carcinoma.