Bcl-2 is overexpressed and alters the threshold for apoptosis in a cholangiocarcinoma cell line
Identifieur interne : 003D89 ( Main/Exploration ); précédent : 003D88; suivant : 003D90Bcl-2 is overexpressed and alters the threshold for apoptosis in a cholangiocarcinoma cell line
Auteurs : Dm Harnois [États-Unis] ; Fg Que [États-Unis] ; A. Celli [États-Unis] ; Nf Larusso [États-Unis] ; Gj Gores [États-Unis]Source :
- Hepatology [ 0270-9139 ] ; 1997.
English descriptors
- Teeft :
- Antisense, Antisense oligonucleotide, Antisense oligonucleotides, Apoptosis, Beauvericin, Cell death, Cell growth, Cell line, Cell lines, Cell lysates, Cholangiocarcinoma, Cholangiocarcinoma cell line, Cholangiocarcinoma cells, Cholangiocarcinomas, Cholangiocyte, Cholangiocytes, Cultured cells, Dmem media, Dysregulation, Family members, Harnois, Hepa, Hepatology, Hepatology hepatology, Hepatology october, Immunoblot, Immunoblot analysis, Laser densitometry, Malignant, Malignant cell line, Malignant cells, Malignant cholangiocytes, Malignant transformation, Monoclonal antibody, Nonmalignant, Nonmalignant cell line, Nonmalignant cell lines, Nonmalignant cells, Nonmalignant cholangiocytes, Nuclear fragmentation, Nude mice, Oligonucleotide, Oligonucleotides, Peroxidase conjugate antibody, Phenotype, Phenotypic, Protein expression, Protein product, Room temperature, Secondary antibody, Simian virus, Vector laboratories.
Abstract
Abstract: Cholangiocarcinoma is a malignant neoplasm originating from cholangiocytes. The mechanisms responsible for oncogenesis of cholangiocytes are unknown. Resistance to apoptosis, especially by altered expression of B-cell lymphoma/leukemia 2 (Bcl-2) family members, has been implicated as a mechanism contributing to malignant transformation. Thus, our aim was to test the hypothesis that altered expression of Bcl-2 family members by cholangiocarcinoma cells renders them resistant to apoptosis. We compared the apoptotic threshold and expression of the Bcl-2 protein family members, Bcl-2, Bcl-XL, and Bax, in two human cell lines: 1) nonmalignant human cholangiocytes immortalized by transfection with the simian virus 40 (SV 40) large T antigen; and 2) a malignant human cholangiocarcinoma cell line. Apoptosis was induced pharmacologically using beauvericin. Bcl-2, Bcl-x long, and Bax protein expression were evaluated by immunoblot analysis, and Bcl-2 expression was modulated using antisense technology. The cholangiocyte and malignant/nonmaligant phenotype of both cell lines was verified using both in vitro and in vivo approaches. Beauvericin induced apoptosis of nonmalignant cholangiocytes in a concentration- (0 to 25 micromol/L) and time- (0 to 6 hours) dependent manner. In contrast, malignant cholangiocytes were resistant to apoptosis. Although expression of Bcl-x long and Bax protein were similiar in the two cell lines, Bcl-2 protein expression was 15-fold greater in malignant than in nonmalignant cholangiocytes. An 18 mer bcl-2 antisense oligonucleotide reduced expression of Bcl-2 protein by 50% and increased the rate of beauvericin-induced apoptosis more than threefold in the malignant cells. Our results support the hypothesis that resistance to apoptosis by overexpression of Bcl-2 may be a feature of cholangiocarcinoma. (Hepatology 1997 Oct;26(4):884-90)
Url:
DOI: 10.1053/jhep.1997.v26.pm0009328309
Affiliations:
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Celli</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Internal Medicine, Mayo Medical School, Clinic and Foundation, Rochester, MN 55905</wicri:regionArea><wicri:noRegion>MN 55905</wicri:noRegion></affiliation></author><author><name sortKey="Larusso, Nf" sort="Larusso, Nf" uniqKey="Larusso N" first="Nf" last="Larusso">Nf Larusso</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Internal Medicine, Mayo Medical School, Clinic and Foundation, Rochester, MN 55905</wicri:regionArea><wicri:noRegion>MN 55905</wicri:noRegion></affiliation></author><author><name sortKey="Gores, Gj" sort="Gores, Gj" uniqKey="Gores G" first="Gj" last="Gores">Gj Gores</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Internal Medicine, Mayo Medical School, Clinic and Foundation, Rochester, MN 55905</wicri:regionArea><wicri:noRegion>MN 55905</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Hepatology</title><title level="j" type="abbrev">YJHEP</title><idno type="ISSN">0270-9139</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1997">1997</date><biblScope unit="volume">26</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="884">884</biblScope><biblScope unit="page" to="890">890</biblScope></imprint><idno type="ISSN">0270-9139</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0270-9139</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Antisense</term><term>Antisense oligonucleotide</term><term>Antisense oligonucleotides</term><term>Apoptosis</term><term>Beauvericin</term><term>Cell death</term><term>Cell growth</term><term>Cell line</term><term>Cell lines</term><term>Cell lysates</term><term>Cholangiocarcinoma</term><term>Cholangiocarcinoma cell line</term><term>Cholangiocarcinoma cells</term><term>Cholangiocarcinomas</term><term>Cholangiocyte</term><term>Cholangiocytes</term><term>Cultured cells</term><term>Dmem media</term><term>Dysregulation</term><term>Family members</term><term>Harnois</term><term>Hepa</term><term>Hepatology</term><term>Hepatology hepatology</term><term>Hepatology october</term><term>Immunoblot</term><term>Immunoblot analysis</term><term>Laser densitometry</term><term>Malignant</term><term>Malignant cell line</term><term>Malignant cells</term><term>Malignant cholangiocytes</term><term>Malignant transformation</term><term>Monoclonal antibody</term><term>Nonmalignant</term><term>Nonmalignant cell line</term><term>Nonmalignant cell lines</term><term>Nonmalignant cells</term><term>Nonmalignant cholangiocytes</term><term>Nuclear fragmentation</term><term>Nude mice</term><term>Oligonucleotide</term><term>Oligonucleotides</term><term>Peroxidase conjugate antibody</term><term>Phenotype</term><term>Phenotypic</term><term>Protein expression</term><term>Protein product</term><term>Room temperature</term><term>Secondary antibody</term><term>Simian virus</term><term>Vector laboratories</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Cholangiocarcinoma is a malignant neoplasm originating from cholangiocytes. The mechanisms responsible for oncogenesis of cholangiocytes are unknown. Resistance to apoptosis, especially by altered expression of B-cell lymphoma/leukemia 2 (Bcl-2) family members, has been implicated as a mechanism contributing to malignant transformation. Thus, our aim was to test the hypothesis that altered expression of Bcl-2 family members by cholangiocarcinoma cells renders them resistant to apoptosis. We compared the apoptotic threshold and expression of the Bcl-2 protein family members, Bcl-2, Bcl-XL, and Bax, in two human cell lines: 1) nonmalignant human cholangiocytes immortalized by transfection with the simian virus 40 (SV 40) large T antigen; and 2) a malignant human cholangiocarcinoma cell line. Apoptosis was induced pharmacologically using beauvericin. Bcl-2, Bcl-x long, and Bax protein expression were evaluated by immunoblot analysis, and Bcl-2 expression was modulated using antisense technology. The cholangiocyte and malignant/nonmaligant phenotype of both cell lines was verified using both in vitro and in vivo approaches. Beauvericin induced apoptosis of nonmalignant cholangiocytes in a concentration- (0 to 25 micromol/L) and time- (0 to 6 hours) dependent manner. In contrast, malignant cholangiocytes were resistant to apoptosis. Although expression of Bcl-x long and Bax protein were similiar in the two cell lines, Bcl-2 protein expression was 15-fold greater in malignant than in nonmalignant cholangiocytes. An 18 mer bcl-2 antisense oligonucleotide reduced expression of Bcl-2 protein by 50% and increased the rate of beauvericin-induced apoptosis more than threefold in the malignant cells. Our results support the hypothesis that resistance to apoptosis by overexpression of Bcl-2 may be a feature of cholangiocarcinoma. (Hepatology 1997 Oct;26(4):884-90)</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Harnois, Dm" sort="Harnois, Dm" uniqKey="Harnois D" first="Dm" last="Harnois">Dm Harnois</name></noRegion><name sortKey="Celli, A" sort="Celli, A" uniqKey="Celli A" first="A" last="Celli">A. Celli</name><name sortKey="Gores, Gj" sort="Gores, Gj" uniqKey="Gores G" first="Gj" last="Gores">Gj Gores</name><name sortKey="Larusso, Nf" sort="Larusso, Nf" uniqKey="Larusso N" first="Nf" last="Larusso">Nf Larusso</name><name sortKey="Que, Fg" sort="Que, Fg" uniqKey="Que F" first="Fg" last="Que">Fg Que</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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