| BAD, a proapoptotic member of the BCL2 family, is a potential therapeutic target in hepatocellular carcinoma. | |
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MedLine Citation:
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PMID: 20647330 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Proteins of the BCL2 family are key regulators of apoptosis. Their expression levels are frequently altered in cancers, enabling tumor cells to survive. To gain insight into the pathogenesis of hepatocellular carcinoma (HCC), we performed a comprehensive survey of the expression of the members of the BCL2 family in samples obtained from surgically resected HCCs. Here, we report the occurrence of a new molecular anomaly, consisting of a strong reduction in the expression of the proapoptotic protein BAD in HCC compared with surrounding nontumoral tissue. We investigate the function of BAD in a panel of HCC cell lines. Using gene overexpression and RNA interference, we show that BAD is involved in the cytotoxic effects of sorafenib, a multikinase blocker, which is currently the sole therapeutic drug effective for the treatment of HCC. Finally, we report that ABT-737, a compound that interacts with proteins of the BCL2 family and exhibits a BAD-like reactivity, sensitizes HCC cells toward sorafenib-induced apoptosis. Collectively, our findings indicate that BAD is a key regulator of apoptosis in HCC and an important determinant of HCC cell response to sorafenib. |
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Authors:
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Antoine Galmiche; Zakaria Ezzoukhry; Catherine François; Christophe Louandre; Charles Sabbagh; Eric Nguyen-Khac; Véronique Descamps; Nathalie Trouillet; Corinne Godin; Jean-Marc Regimbeau; Jean-Paul Joly; Jean-Claude Barbare; Gilles Duverlie; Jean-Claude Mazière; Denis Chatelain |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-20 |
Journal Detail:
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Title: Molecular cancer research : MCR Volume: 8 ISSN: 1557-3125 ISO Abbreviation: Mol. Cancer Res. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-18 Completed Date: 2010-12-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101150042 Medline TA: Mol Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 1116-25 Citation Subset: IM |
Affiliation:
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Laboratoire de Biochimie, CHU Nord, Amiens Cedex, France. Galmiche.Antoine@chu-amiens.fr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology Apoptosis / drug effects* Benzenesulfonates / pharmacology Biphenyl Compounds / pharmacology Blotting, Western Carcinoma, Hepatocellular / drug therapy, metabolism*, pathology* Cell Line, Tumor Cell Proliferation / drug effects Drug Synergism Humans Liver / drug effects, metabolism, pathology Liver Neoplasms / drug therapy, metabolism*, pathology* Nitrophenols / pharmacology Piperazines / pharmacology Proto-Oncogene Proteins c-bcl-2 / metabolism* Pyridines / pharmacology RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction Sulfonamides / pharmacology Tumor Markers, Biological / metabolism |
| Chemical | |
Reg. No./Substance:
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0/ABT-737; 0/Antineoplastic Agents; 0/Benzenesulfonates; 0/Biphenyl Compounds; 0/Nitrophenols; 0/Piperazines; 0/Proto-Oncogene Proteins c-bcl-2; 0/Pyridines; 0/RNA, Messenger; 0/Sulfonamides; 0/Tumor Markers, Biological; 0/sorafenib |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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