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 |
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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. 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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.91.19.8772</identifier><identifier>PMID: 8090721</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>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</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1994-09, Vol.91 (19), p.8772-8776</ispartof><rights>Copyright 1994 The National Academy of Sciences of the United States of America</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-ac94754f1ae1a13fa6ba249f28c192b5618b368b517577b636a113db38ac89853</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/91/19.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2365911$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2365911$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53770,53772,57996,58229</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8090721$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><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</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><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.</description><subject>cancer cells</subject><subject>Carcinoma - genetics</subject><subject>Cell growth</subject><subject>Cell lines</subject><subject>Complementary DNA</subject><subject>DNA</subject><subject>DNA, Neoplasm - biosynthesis</subject><subject>DNA, Neoplasm - genetics</subject><subject>Gene Amplification</subject><subject>Gene Deletion</subject><subject>Gene Expression</subject><subject>Genes</subject><subject>Human genetics</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Lymphocytes</subject><subject>man</subject><subject>Medical genetics</subject><subject>Messenger RNA</subject><subject>Plasminogen Activator Inhibitor 1 - genetics</subject><subject>Receptors</subject><subject>Receptors, Transforming Growth Factor beta - genetics</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>stomach</subject><subject>Stomach Neoplasms - genetics</subject><subject>Transforming Growth Factor beta - pharmacology</subject><subject>transforming growth factor- beta</subject><subject>transforming growth factor- beta receptors</subject><subject>Tumor Cells, Cultured</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAAhC0EKkvhzAWQT_wcsrXjxLERFxSx6UqVkGA5W47rbFwldrCdln0pDn2QPhMJu13gwsmH-WbG9gDwHKMlRgU5G6wMS46XmC9ZUaQPwAIjjhOacfQQLBBKi4RlafYYPAnhCiHEc4ZOwAlDHBUpXoCflbY6GgXLVtqtDtBYGFsNN17a0DjfG7uFlXc3sYUrqaLz8O4Wvt1Uq-Tu9h3c7AYN12v4RSs9zOIcN2ecj720sJIh-jlcWqU9LHXXhfewdN7rTkbjLLwxU_BXbYOJ5trEHYzuvm5tW1Ob31S9g_vGp-BRI7ugnx3OU_Bt9WlTnicXn6t1-fEiURknMZGKZ0WeNVhqLDFpJK1lmvEmZQrztM4pZjWhrM5xkRdFTQmVGJPLmjCpGGc5OQUf9rnDWPf6UmkbvezE4E0v_U44acS_ijWt2LprkWWUscn--mD37vuoQxS9CWp6vbTajUFgSknK8hk824PKuxC8bo4VGIl5YDEPLDgWmIt54Mnx8u-bHfnDopP-5qDPxnv1T4Boxq6L-kecyFf_JSfgxR64CtO0RyIlNOfTd_0C_XjHQw</recordid><startdate>19940913</startdate><enddate>19940913</enddate><creator>Park, Keunchil</creator><creator>Kim, Seong-Jin</creator><creator>Bang, Yung-Jue</creator><creator>Park, Jae-Gahb</creator><creator>Kim, Noe Kyeong</creator><creator>Roberts, Anita B.</creator><creator>Sporn, Michael B.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T3</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>19940913</creationdate><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</title><author>Park, Keunchil ; 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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