Apoptosis and APC in Colorectal Tumorigenesis
Tumors result from disruptions in the homeostatic mechanisms that regulate cell birth and cell death. In colon cancer, one of the earliest manifestation of this imbalance is the formation of polyps, caused by somatic and inherited mutations of the adenomatous polyposis coli (APC) tumor suppressor ge...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1996-07, Vol.93 (15), p.7950-7954 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Morin, Patrice J. Vogelstein, Bert Kinzler, Kenneth W. |
| description | Tumors result from disruptions in the homeostatic mechanisms that regulate cell birth and cell death. In colon cancer, one of the earliest manifestation of this imbalance is the formation of polyps, caused by somatic and inherited mutations of the adenomatous polyposis coli (APC) tumor suppressor gene in both humans and mice. While the importance of APC in tumorigenesis is well documented, how it functions to prevent tumors remains a mystery. Using a novel inducible expression system, we show that expression of APC in human colorectal cancer cells containing endogenous inactive APC alleles results in a substantial diminution of cell growth. Further evaluation demonstrated that this was due to the induction of cell death through apoptosis. These results suggest that apoptosis plays a role not only in advanced tumors but also at the very earliest stages of neoplasia. |
| doi_str_mv | 10.1073/pnas.93.15.7950 |
| format | Article |
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In colon cancer, one of the earliest manifestation of this imbalance is the formation of polyps, caused by somatic and inherited mutations of the adenomatous polyposis coli (APC) tumor suppressor gene in both humans and mice. While the importance of APC in tumorigenesis is well documented, how it functions to prevent tumors remains a mystery. Using a novel inducible expression system, we show that expression of APC in human colorectal cancer cells containing endogenous inactive APC alleles results in a substantial diminution of cell growth. Further evaluation demonstrated that this was due to the induction of cell death through apoptosis. 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In colon cancer, one of the earliest manifestation of this imbalance is the formation of polyps, caused by somatic and inherited mutations of the adenomatous polyposis coli (APC) tumor suppressor gene in both humans and mice. While the importance of APC in tumorigenesis is well documented, how it functions to prevent tumors remains a mystery. Using a novel inducible expression system, we show that expression of APC in human colorectal cancer cells containing endogenous inactive APC alleles results in a substantial diminution of cell growth. Further evaluation demonstrated that this was due to the induction of cell death through apoptosis. These results suggest that apoptosis plays a role not only in advanced tumors but also at the very earliest stages of neoplasia.</description><subject>Adenomatous Polyposis Coli Protein</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Base Sequence</subject><subject>Cell Division</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Cytoskeletal Proteins - biosynthesis</subject><subject>Epithelial cells</subject><subject>Gene Expression</subject><subject>Genes, APC</subject><subject>HT29 cells</subject><subject>Humans</subject><subject>Inductive reasoning</subject><subject>Introns</subject><subject>Kinetics</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Oligodeoxyribonucleotides</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Restriction Mapping</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Zinc</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1LwzAchoMoc07PgqD0pKduvyRNk4KXMfyCgR52D1mazo62qUkr-t_bsjr0oqcc3ud5SfIidI5hioHTWV0pP03oFLMpTxgcoDGGBIdxlMAhGgMQHoqIRMfoxPstACRMwAiNBGeMCTpG4by2dWN97gNVpcH8ZRHkVbCwhXVGN6oIVm1pXb4xlemYU3SUqcKbs-GcoNX93WrxGC6fH54W82WoGeNNSAUhhiqGM6NAqZQQEmsKGSZrwanAmsXCYLZOudZJzHiPZUQzKjhgSOkE3e5q63ZdmlSbqnGqkLXLS-U-pVW5_J1U-avc2HdJhWCs068H3dm31vhGlrnXpihUZWzrJRckTqIo_hfELKac8L5xtgO1s947k-3vgkH2O8h-B5nQTpH9Dp1x-fMJe374-C6_GvJe_E5_Fdz8CcisLYrGfDQdebEjt76xbo9GgCNKvwCYxqTP</recordid><startdate>19960723</startdate><enddate>19960723</enddate><creator>Morin, Patrice J.</creator><creator>Vogelstein, Bert</creator><creator>Kinzler, Kenneth W.</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>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19960723</creationdate><title>Apoptosis and APC in Colorectal Tumorigenesis</title><author>Morin, Patrice J. ; Vogelstein, Bert ; Kinzler, Kenneth W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-3822e3a51fea0aad2226c30f12b87381c568e15bd7cc9657fea0f2c5387010d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adenomatous Polyposis Coli Protein</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Base Sequence</topic><topic>Cell Division</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Cell lines</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Cytoskeletal Proteins - biosynthesis</topic><topic>Epithelial cells</topic><topic>Gene Expression</topic><topic>Genes, APC</topic><topic>HT29 cells</topic><topic>Humans</topic><topic>Inductive reasoning</topic><topic>Introns</topic><topic>Kinetics</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>Oligodeoxyribonucleotides</topic><topic>Plasmids</topic><topic>Proteins</topic><topic>Recombinant Proteins - biosynthesis</topic><topic>Restriction Mapping</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><topic>Zinc</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morin, Patrice J.</creatorcontrib><creatorcontrib>Vogelstein, Bert</creatorcontrib><creatorcontrib>Kinzler, Kenneth W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</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>Morin, Patrice J.</au><au>Vogelstein, Bert</au><au>Kinzler, Kenneth W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apoptosis and APC in Colorectal Tumorigenesis</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1996-07-23</date><risdate>1996</risdate><volume>93</volume><issue>15</issue><spage>7950</spage><epage>7954</epage><pages>7950-7954</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Tumors result from disruptions in the homeostatic mechanisms that regulate cell birth and cell death. 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| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1996-07, Vol.93 (15), p.7950-7954 |
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| language | eng |
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| source | MEDLINE; Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adenomatous Polyposis Coli Protein Animals Apoptosis Base Sequence Cell Division Cell growth Cell Line Cell lines Colonic Neoplasms - genetics Colonic Neoplasms - pathology Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Cytoskeletal Proteins - biosynthesis Epithelial cells Gene Expression Genes, APC HT29 cells Humans Inductive reasoning Introns Kinetics Mice Molecular Sequence Data Oligodeoxyribonucleotides Plasmids Proteins Recombinant Proteins - biosynthesis Restriction Mapping Transfection Tumor Cells, Cultured Tumors Zinc |
| title | Apoptosis and APC in Colorectal Tumorigenesis |
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