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Growth Inhibition of Transforming Growth Factor ß on Human Gastric Carcinoma Cells: Receptor and Postreceptor Signaling¹

First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan

The effect of transforming growth factor ß (TGF-ß) on human gastric carcinoma cell lines was examined. Cell growth and DNA synthesis of TMK-1 were inhibited by TGF-ß, whereas MKN-28 presented no response to TGF-ß. Scatchard plot analysis of TGF-ß binding showed that TMK-1 had a relatively small number of high-affinity receptors, whereas MKN-28 had a large number of low-affinity receptors. By affinity labeling, only the type I receptor (M_r 65,000) for TGF-ß was detected in TMK-1, while three types of receptors, type I, type II (M_r 85,000–95,000), and type III (M_r 250,000–350,000), for TGF-ß were present in MKN-28. TGF-ß treatment reduced p34^cdc-2 kinase activity and the level of phosphorylation of retinoblastoma protein in TMK-1, whereas it did not affect them in MKN-28. mRNAs for MYC and platelet-derived growth factor B chain were increased by treatment of TGF-ß on TMK-1. cAMP-responsive element binding activity was decreased by TGF-ß treatment in MKN-28 but not in TMK-1. This was closely correlated with protein kinase C activity.

These results suggest that the type I receptor for TGF-ß in human gastric carcinoma cells may be mainly linked with the growth inhibition of TGF-ß by a decrease in retinoblastoma protein phosphorylation by p34^cdc-2 without suppression of MYC expression. Conversely, TGF-ß may reduce protein kinase C activity and cAMP-responsive element binding activity in TGF-ß-resistant gastric carcinoma cells.

¹ Supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare for a Comprehensive 10-Year Strategy for Cancer Control and from the Ministry of Education, Science and Culture, Japan.

² To whom requests for reprints should be addressed.

Received 7/ 8/91. Accepted 11/13/91.

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