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Down-regulation of mitochondrial F1F0-ATP synthase in human colon cancer cells with induced 5-fluorouracil resistance
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Shin, Young-Kyoung | - |
dc.contributor.author | Yoo, Byong Chul | - |
dc.contributor.author | Chang, Hee Jin | - |
dc.contributor.author | Jeon, Eunkyung | - |
dc.contributor.author | Hong, Sung-Hye | - |
dc.contributor.author | Jung, Mi-Sun | - |
dc.contributor.author | Lim, Soo-Jeong | - |
dc.contributor.author | Park, Jae-Gahb | - |
dc.date.accessioned | 2009-11-09T06:21:33Z | - |
dc.date.available | 2009-11-09T06:21:33Z | - |
dc.date.issued | 2005-04-19 | - |
dc.identifier.citation | Cancer Res. 2005 Apr 15;65(8):3162-70 | en |
dc.identifier.issn | 0008-5472 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15833846 | - |
dc.identifier.uri | https://hdl.handle.net/10371/11585 | - |
dc.description.abstract | 5-Fluorouracil (5-FU) is widely used for treatment of advanced colorectal cancer. However, it is common for such patients to develop resistance to 5-FU, and this drug resistance becomes a critical problem for chemotherapy. The mechanisms underlying this resistance are largely unknown. To screen for proteins possibly responsible for 5-FU resistance, cells resistant to 5-FU were derived from human colon cancer cell lines and two-dimensional gel electrophoresis-based comparative proteomics was done. Two-dimensional gel electrophoresis data showed there was lower expression of the alpha subunit of mitochondrial F(1)F(0)-ATP synthase (ATP synthase) in 5-FU-resistant cells compared with parent cells. Western blotting showed that expression of other ATP synthase complex subunits was also lower in 5-FU-resistant cell lines and that these resistant cells also showed decreased ATP synthase activity and reduced intracellular ATP content. The ATP synthase inhibitor, oligomycin A, strongly antagonized 5-FU-induced suppression of cell proliferation. When 5-FU sensitivity was compared with ATP synthase activity in six different human colon cancer cell lines, a positive correlation has been found. Furthermore, suppressed ATP synthase d-subunit expression by siRNA transfection increased cell viability in the presence of 5-FU. Bioenergetic dysfunction of mitochondria has been reported as a hallmark of many types of cancers (i.e., down-regulation of ATP synthase beta-subunit expression in liver, kidney, colon, squamous oesophageal, and lung carcinomas, as well as in breast and gastric adenocarcinomas). Our findings show that ATP synthase down-regulation may not only be a bioenergetic signature of colorectal carcinomas but may also lead to cellular events responsible for 5-FU resistance. | en |
dc.language.iso | en | en |
dc.publisher | American Association for Cancer Research | en |
dc.subject | Antimetabolites, Antineoplastic/*pharmacology | en |
dc.subject | Aurovertins/pharmacology | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Cell Proliferation/drug effects | en |
dc.subject | Colonic Neoplasms/*drug therapy/*enzymology/genetics | en |
dc.subject | Down-Regulation | en |
dc.subject | Drug Resistance, Neoplasm | en |
dc.subject | Energy Metabolism | en |
dc.subject | Enzyme Inhibitors/pharmacology | en |
dc.subject | Fluorouracil/*pharmacology | en |
dc.subject | Humans | en |
dc.subject | Mitochondria/*enzymology | en |
dc.subject | Mitochondrial Proton-Translocating ATPases/*antagonists & | en |
dc.subject | inhibitors/biosynthesis/genetics | en |
dc.subject | Oligomycins/pharmacology | en |
dc.subject | RNA, Small Interfering/genetics | en |
dc.subject | Transfection | en |
dc.title | Down-regulation of mitochondrial F1F0-ATP synthase in human colon cancer cells with induced 5-fluorouracil resistance | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 신영경 | - |
dc.contributor.AlternativeAuthor | 유병철 | - |
dc.contributor.AlternativeAuthor | 장희진 | - |
dc.contributor.AlternativeAuthor | 전은경 | - |
dc.contributor.AlternativeAuthor | 홍성혜 | - |
dc.contributor.AlternativeAuthor | 정미선 | - |
dc.contributor.AlternativeAuthor | 임수정 | - |
dc.contributor.AlternativeAuthor | 박재갑 | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-04-3300 | - |
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