Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arachidonic acid metabolism plays an important role in colon carcinogenesis. Cyclooxygenase-2 (COX-2), which catalyzes the rate-limiting step in the synthesis of prostaglandins from arachidonic acids, is known to be up-regulated in colon cancer, and multiple lines of evidence indicate that it is a critical early step in colon carcinogenesis. Recently, 15-lipoxygenase-1, the enzyme that converts arachidonic acid to 15(S)-HETE, was also found to be up-regulated in colon carcinoma. In our previous studies, we cloned a gene that encodes another arachidonic acid-using enzyme, fatty acid CoA ligase 4 (FACL4), and showed that overexpression of this enzyme prevents apoptosis. We have also showed that FACL4 and COX-2 synergistically inhibit apoptosis by reducing the intracellular level of free arachidonic acid. Here, we report that expression of FACL4 is significantly increased in colon adenocarcinoma compared with adjacent normal tissue at both the mRNA and protein levels by quantitative RT-PCR (paired t test, P < 0.015), immunoblot, and immunohistochemical staining. We found that the increase in expression level of FACL4 mRNA relative to control ranged between 2.4- and 54.5-fold; the average fold-increase was 13.4. The increase in FACL4 protein expression is between 2.4- and 65.0-fold. In addition, we found that a higher level of increased FACL4 expression was correlated with well and moderately differentiated adenocarcinoma, whereas no similar correlation was observed with COX-2 expression. The in situ hybridization results indicate that expression of FACL4 is localized predominantly in the colon epithelium but not in the stroma. The onset of FACL4 up-regulation appears to occur during the transformation from adenoma to adenocarcinoma because FACL4 expression was not increased above normal in the three colon adenomas examined. Finally, we observed that a tumor promoter significantly induced FACL4 expression. These findings suggest that the FACL4 pathway may be important in colon carcinogenesis, and that the development of selective inhibitors for FACL4 may be a worthy effort in the prevention and treatment of colon cancer.
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PMID:Fatty acid CoA ligase 4 is up-regulated in colon adenocarcinoma. 1173 23

Several pathways of fatty acid metabolism have been shown to be associated with the pathogenesis of colorectal cancer. Fatty acid acyl-CoA thioesters are formed from free fatty acids and coenzyme A by the activity of acyl-CoA synthetases (ACSs). Whilst an increase in ACS4 expression has been associated with colorectal carcinogenesis, little is known about possible pathogenetic functions of other ACS isoforms, such as ACS5, in tumourigenesis. In the present study, gene expression, protein synthesis, and enzymatic activity of ACS5 in sporadic colorectal adenocarcinomas, adenomas, and established cell lines were analysed using RT-PCR, western blot analysis, immunofluorescence, and an enzymatic assay. Enhanced expression of ACS5 mRNA and protein as well as enzymatic activity was found in adenomas and in 11 (73%; group 1) of 15 colorectal adenocarcinomas investigated, while a decrease of ACS5 was seen in four tumours (27%; group 2). However, basal ACS5 enzymatic activity was increased as a percentage of the total activity of ACSs in both groups, arguing for an absolute (group 1) or relative (group 2) increase in ACS5 enzymatic activity in all adenocarcinomas investigated. These findings are reflected by in vitro analysis of three established colorectal adenocarcinoma cell lines, in which activity of ACS5 occurred. The results suggest the involvement of ACS5 in the early genesis of colorectal cancer, most likely by modification of the transport and pool formation of long-chain acyl-CoA thioesters, as recently demonstrated for other isoforms of the ACS family.
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PMID:Impaired expression of acyl-CoA synthetase 5 in sporadic colorectal adenocarcinomas. 1611 Apr 57

A number of epidemiologic studies have indicated a strong association between dietary fat intake and prostate cancer development, suggesting that lipid metabolism plays some important roles in prostate carcinogenesis and its progression. In this study, through our genome-wide gene expression analysis of clinical prostate cancer cells, we identified a novel lipogenic gene, ELOVL7, coding a possible long-chain fatty acid elongase, as overexpressed in prostate cancer cells. ELOVL7 expression is regulated by the androgen pathway through SREBP1, as well as other lipogenic enzymes. Knockdown of ELOVL7 resulted in drastic attenuation of prostate cancer cell growth, and it is notable that high-fat diet promoted the growth of in vivo tumors of ELOVL7-expressed prostate cancer. In vitro fatty acid elongation assay and fatty acid composition analysis indicated that ELOVL7 was preferentially involved in fatty acid elongation of saturated very-long-chain fatty acids (SVLFA, C20:0 approximately ). Lipid profiles showed that knockdown of ELOVL7 in prostate cancer cells affected SVLFAs in the phospholipids and the neutral lipids, such as cholesterol ester. Focusing on cholesterol ester as a source of de novo steroid synthesis, we show that ELOVL7 affected de novo androgen synthesis in prostate cancer cells. These findings suggest that EVOLV7 could be involved in prostate cancer growth and survival through the metabolism of SVLFAs and their derivatives, could be a key molecule to elucidate the association between fat dietary intake and prostate carcinogenesis, and could also be a promising molecular target for development of new therapeutic or preventive strategies for prostate cancers.
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PMID:Novel lipogenic enzyme ELOVL7 is involved in prostate cancer growth through saturated long-chain fatty acid metabolism. 1982 53