Genetic changes in the transforming growth factor β (TGF-β) type II receptor gene in human gastric cancer cells: Correlation with sensitivity to growth inhibition by TGF-β

Keunchil Park, Seong Jin Kim, Yung Jue Bang, Jae Gahb Park, Noe Kyeong Kim, Anita B. Roberts, Michael B. Sporn

Research output: Contribution to journalArticle

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Abstract

We have found several genetic changes in the TGF-β type II receptor gene in human gastric cancer cell lines resistant to the growth inhibitory effect of TGF-β. Southern blot analysis showed deletion of the type II receptor gene in two of eight cell lines and amplification in another two lines. The single cell line we studied that is sensitive to growth inhibition by TGF-β showed no structural abnormalities of the type II receptor gene. Some of the gastric cancer cells resistant to the growth inhibitory effect of TGF-β express either truncated or no detectable TGF-β type II receptor mRNAs, whereas the one that retains responsiveness to the growth inhibitory effect of TGF-β expresses a full-size type II receptor mRNA. Immunoprecipitation followed by Western blot analysis showed parallel changes in TGF-β type II receptor expression. Our results suggest that one of the possible mechanisms of escape from autocrine or paracrine growth control by TGF-β during carcinogenesis could involve genetic changes in the TGF-β type II receptor gene itself or altered expression of its mRNA.

Original languageEnglish
Pages (from-to)8772-8776
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number19
DOIs
StatePublished - 13 Sep 1994

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Growth Factor Receptors
Transforming Growth Factors
Stomach Neoplasms
Growth
Genes
Cell Line
Messenger RNA
Southern Blotting
Immunoprecipitation
Carcinogenesis
Western Blotting

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abstract = "We have found several genetic changes in the TGF-β type II receptor gene in human gastric cancer cell lines resistant to the growth inhibitory effect of TGF-β. Southern blot analysis showed deletion of the type II receptor gene in two of eight cell lines and amplification in another two lines. The single cell line we studied that is sensitive to growth inhibition by TGF-β showed no structural abnormalities of the type II receptor gene. Some of the gastric cancer cells resistant to the growth inhibitory effect of TGF-β express either truncated or no detectable TGF-β type II receptor mRNAs, whereas the one that retains responsiveness to the growth inhibitory effect of TGF-β expresses a full-size type II receptor mRNA. Immunoprecipitation followed by Western blot analysis showed parallel changes in TGF-β type II receptor expression. Our results suggest that one of the possible mechanisms of escape from autocrine or paracrine growth control by TGF-β during carcinogenesis could involve genetic changes in the TGF-β type II receptor gene itself or altered expression of its mRNA.",
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Genetic changes in the transforming growth factor β (TGF-β) type II receptor gene in human gastric cancer cells : Correlation with sensitivity to growth inhibition by TGF-β. / Park, Keunchil; Kim, Seong Jin; Bang, Yung Jue; Park, Jae Gahb; Kim, Noe Kyeong; Roberts, Anita B.; Sporn, Michael B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 19, 13.09.1994, p. 8772-8776.

Research output: Contribution to journalArticle

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AU - Roberts, Anita B.

AU - Sporn, Michael B.

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