Novel Lipogenic Enzyme ELOVL7 Is Involved in Prostate Cancer Growth through Saturated Long-Chain Fatty Acid Metabolism

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 analysi...

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Bibliographic Details
Published in:	Cancer research (Chicago, Ill.) Vol. 69; no. 20; pp. 8133 - 8140
Main Authors:	TAMURA, Kenji, MAKINO, Asami, NAKAMURA, Yusuke, NAKAGAWA, Hidewaki, HULLIN-MATSUDA, Françoise, KOBAYASHI, Toshihide, FURIHATA, Mutsuo, CHUG, Suyoun, ASHIDA, Shingo, MIKI, Tsuneharu, FUJIOKA, Tomoaki, SHUIN, Taro
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 15-10-2009
Subjects:	Acetyltransferases - physiology Androgens - pharmacology Animals Antineoplastic agents Biological and medical sciences Biomarkers, Tumor Blotting, Northern Chromatography, Liquid Dietary Fats Fatty Acids - metabolism Gas Chromatography-Mass Spectrometry Gene Expression Profiling Gene Expression Regulation, Neoplastic Gynecology. Andrology. Obstetrics Humans Immunoglobulin G - immunology Lipid Metabolism Male Male genital diseases Medical sciences Mice Mice, Nude Molecular Sequence Data Neoplasms, Hormone-Dependent - metabolism Neoplasms, Hormone-Dependent - pathology Nephrology. Urinary tract diseases Oligonucleotide Array Sequence Analysis Peptide Fragments - metabolism Pharmacology. Drug treatments Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Rabbits Sterol Regulatory Element Binding Protein 1 - genetics Sterol Regulatory Element Binding Protein 1 - metabolism Tandem Mass Spectrometry Tumor Cells, Cultured Tumors Tumors of the urinary system Urinary tract. Prostate gland Xenograft Model Antitumor Assays Urinary system disease Prostate disease Growth Enzyme Long chain Lipids Malignant tumor Metabolism Fatty acids Pharmacokinetics Male genital diseases Prostate cancer Cancer
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Summary:	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.
ISSN:	0008-5472 1538-7445
DOI:	10.1158/0008-5472.CAN-09-0775