Reduced levels of transforming growth factor-beta type I receptor in human gastric carcinomas.
The expressions of transforming growth factor beta (TGF-beta) and its receptor and TGF-beta inhibitory element (TIE)-binding protein were examined on human gastric carcinomas by Northern blot hybridization, immunohistochemistry, affinity labeling and gel retardation analysis. TGF-beta mRNA was expressed in tumor and normal tissues at various levels. Immunohistochemically, TGF-beta 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-beta 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-beta, had only type I receptor for TGF-beta and showed a high level of TIE-binding protein. Conversely, MKN-1, a TGF-beta-resistant cell line, exhibited an extremely low level of TGF-beta receptor and had no TIE-binding protein. These results overall indicate that although human gastric carcinoma cells produced TGF-beta, they showed a reduction in TGF-beta type I receptor and a low level of TIE-binding protein, resulting in escape from growth inhibition by TGF-beta.
Ito
M
M
First Department of Pathology, Hiroshima University School of Medicine.
Yasui
W
W
Nakayama
H
H
Yokozaki
H
H
Ito
H
H
Tahara
E
E
D000368:Aged; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line / Q000378:metabolism; D004261:DNA Replication; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000032:analysis*; D018125:Receptors, Transforming Growth Factor beta; D013274:Stomach Neoplasms / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000032:analysis*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta