Reduced Levels of Transforming Growth Factor‐beta Type I Receptor in Human Gastric Carcinomas

The expressions of transforming growth factor beta (TGF‐β) and its receptor and TGF‐β inhibitory element (TIE)‐binding protein were examined on human gastric carcinomas by Northern blot hybridization, immunohistochemistry, affinity labeling and gel retardation analysis. TGF‐β mRNA was expressed in tumor and normal tissues at various levels. Immunohistochemically, TGF‐β expression was confirmed to be present within tumor cells. Out of the 17 human gastric carcinoma tissues, 14 (82%) showed a reduction in the level of type I receptor (65 kDa) for TGF‐β when compared to corresponding normal mucosas. Interestingly, in seven of the 14 tumors the level of TIE‐binding protein in the tumor tissue was lower than that in normal mucosa. Human gastric carcinoma cell line TMK‐1, whose growth was inhibited by TGF‐β, had only type I receptor for TGF‐β and showed a high level of TIE‐binding protein. Conversely, MKN‐1, a TGF‐β ‐resistant cell line, exhibited an extremely low level of TGF‐β receptor and had no TIE‐binding protein. These results overall indicate that although human gastric carcinoma cells produced TGF‐β, they showed a reduction in TGF‐β type I receptor and a low level of TIE‐binding protein, resulting in escape from growth inhibition by TGF‐β.