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

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 s...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1994-09, Vol.91 (19), p.8772-8776
Hauptverfasser: Park, Keunchil, Kim, Seong-Jin, Bang, Yung-Jue, Park, Jae-Gahb, Kim, Noe Kyeong, Roberts, Anita B., Sporn, Michael B.
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container_end_page 8776
container_issue 19
container_start_page 8772
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 91
creator Park, Keunchil
Kim, Seong-Jin
Bang, Yung-Jue
Park, Jae-Gahb
Kim, Noe Kyeong
Roberts, Anita B.
Sporn, Michael B.
description 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.
doi_str_mv 10.1073/pnas.91.19.8772
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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. 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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. 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Kim, Seong-Jin ; Bang, Yung-Jue ; Park, Jae-Gahb ; Kim, Noe Kyeong ; Roberts, Anita B. ; Sporn, Michael B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-ac94754f1ae1a13fa6ba249f28c192b5618b368b517577b636a113db38ac89853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>cancer cells</topic><topic>Carcinoma - genetics</topic><topic>Cell growth</topic><topic>Cell lines</topic><topic>Complementary DNA</topic><topic>DNA</topic><topic>DNA, Neoplasm - biosynthesis</topic><topic>DNA, Neoplasm - genetics</topic><topic>Gene Amplification</topic><topic>Gene Deletion</topic><topic>Gene Expression</topic><topic>Genes</topic><topic>Human genetics</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Lymphocytes</topic><topic>man</topic><topic>Medical genetics</topic><topic>Messenger RNA</topic><topic>Plasminogen Activator Inhibitor 1 - genetics</topic><topic>Receptors</topic><topic>Receptors, Transforming Growth Factor beta - genetics</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>stomach</topic><topic>Stomach Neoplasms - genetics</topic><topic>Transforming Growth Factor beta - pharmacology</topic><topic>transforming growth factor- beta</topic><topic>transforming growth factor- beta receptors</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Keunchil</creatorcontrib><creatorcontrib>Kim, Seong-Jin</creatorcontrib><creatorcontrib>Bang, Yung-Jue</creatorcontrib><creatorcontrib>Park, Jae-Gahb</creatorcontrib><creatorcontrib>Kim, Noe Kyeong</creatorcontrib><creatorcontrib>Roberts, Anita B.</creatorcontrib><creatorcontrib>Sporn, Michael B.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Human Genome Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Keunchil</au><au>Kim, Seong-Jin</au><au>Bang, Yung-Jue</au><au>Park, Jae-Gahb</au><au>Kim, Noe Kyeong</au><au>Roberts, Anita B.</au><au>Sporn, Michael B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1994-09-13</date><risdate>1994</risdate><volume>91</volume><issue>19</issue><spage>8772</spage><epage>8776</epage><pages>8772-8776</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><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.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>8090721</pmid><doi>10.1073/pnas.91.19.8772</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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subjects cancer cells
Carcinoma - genetics
Cell growth
Cell lines
Complementary DNA
DNA
DNA, Neoplasm - biosynthesis
DNA, Neoplasm - genetics
Gene Amplification
Gene Deletion
Gene Expression
Genes
Human genetics
Humans
In Vitro Techniques
Lymphocytes
man
Medical genetics
Messenger RNA
Plasminogen Activator Inhibitor 1 - genetics
Receptors
Receptors, Transforming Growth Factor beta - genetics
RNA
RNA, Messenger - genetics
stomach
Stomach Neoplasms - genetics
Transforming Growth Factor beta - pharmacology
transforming growth factor- beta
transforming growth factor- beta receptors
Tumor Cells, Cultured
title 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
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