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PMID: 8090721 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 19 ·1994-09-13 ·Pages 8772-6

Park K, Kim SJ, Bang YJ, Park JG, Kim NK, Roberts AB, Sporn MB

Abstract

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

MeSH Terms
Carcinoma/genetics DNA, Neoplasm/biosynthesis,genetics Gene Amplification Gene Deletion Gene Expression Genes Humans In Vitro Techniques Plasminogen Activator Inhibitor 1/genetics RNA, Messenger/genetics Receptors, Transforming Growth Factor beta/genetics Stomach Neoplasms/genetics Transforming Growth Factor beta/pharmacology Tumor Cells, Cultured
Chemicals
DNA, Neoplasm Plasminogen Activator Inhibitor 1 RNA, Messenger Receptors, Transforming Growth Factor beta Transforming Growth Factor beta
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Park K
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892.
Kim S J
Bang Y J
Park J G
Kim N K
Roberts A B
Sporn M B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.19.8772
Published
1994-09-13
Pages
8772-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44688
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.91.19.8772 PMC Full Text View journal details
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