| Endogenously produced ganglioside GM3 endows etoposide and doxorubicin resistance by up-regulating Bcl-2 expression in 3LL Lewis lung carcinoma cells. | |
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MedLine Citation:
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PMID: 16571667 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The ganglioside patterns have been shown to dramatically change during cell proliferation and differentiation and in certain cell-cycle phases, brain development, and cancer malignancy. To investigate the significance of the ganglioside GM3 in cancer malignancy, we established GM3-reconstituted cells by transfecting the cDNA of GM3 synthase into a GM3-deficient subclone of the 3LL Lewis lung carcinoma cell line (Uemura, S. (2003) Glycobiology, 13, 207-216). The GM3-reconstituted cells were resistant to apoptosis induced by etoposide and doxorubicin. There were no changes in the expression levels of topoisomerase IIalpha or P-glycoprotein, or in the uptake of doxorubicin between the GM3-reconstituted cells and the mock-transfected cells. To understand the mechanism of the etoposide-resistant phenotype acquired in the GM3-reconstituted cells, we investigated their apoptotic signaling. Although no difference was observed in the phosphorylation of p53 at serine-15-residue site by etoposide between the GM3-reconstituted cells and mock-transfected cells, the activation of both caspase-3 and caspase-9 was specifically inhibited in the former. We found that the anti-apoptotic protein B-cell leukemia/lymphoma 2 (Bcl-2) was increased in the GM3-reconstituted cells. Moreover, wild-type 3LL Lewis lung carcinoma cells, which have an abundance of GM3, exhibited no DNA fragmentation following etoposide treatment and expressed higher levels of the Bcl-2 protein compared with the J5 subclone. Thus, these results support the conclusion that endogenously produced GM3 is involved in malignant phenotypes, including anticancer drug resistance through up-regulating the Bcl-2 protein in this lung cancer cell line. |
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Authors:
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Mariko Noguchi; Kazuya Kabayama; Satoshi Uemura; Byoung-won Kang; Masaki Saito; Yasuyuki Igarashi; Jin-ichi Inokuchi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-03-29 |
Journal Detail:
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Title: Glycobiology Volume: 16 ISSN: 0959-6658 ISO Abbreviation: Glycobiology Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-06-16 Completed Date: 2006-08-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9104124 Medline TA: Glycobiology Country: England |
Other Details:
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Languages: eng Pagination: 641-50 Citation Subset: IM |
Affiliation:
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Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / pharmacology* Apoptosis Carcinoma, Lewis Lung / metabolism* Caspase 3 Caspase 9 Caspases / antagonists & inhibitors Ceramides / metabolism Doxorubicin / pharmacology* Drug Resistance, Neoplasm Etoposide / pharmacology* G(M3) Ganglioside / metabolism* Mice P-Glycoprotein / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism* Receptors, Tumor Necrosis Factor / physiology Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Ceramides; 0/G(M3) Ganglioside; 0/P-Glycoprotein; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Tumor Necrosis Factor; 23214-92-8/Doxorubicin; 33419-42-0/Etoposide; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Casp9 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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