Expression of Long-chain Fatty Acyl-CoA Synthetase 4 in Breast and Prostate Cancers Is Associated with Sex Steroid Hormone Receptor Negativity
Expression of Long-chain Fatty Acyl-CoA Synthetase 4 in Breast and Prostate Cancers Is Associated with Sex Steroid Hormone Receptor Negativity
复制标题
DOI：
10.1593/tlo.09202
复制
发表时间：
2010-04-01
影响因子：
5
通讯作者：
Stafforini, Diana M.
中科院分区：
文献类型：
--
作者：
Monaco, Marie E.;Creighton, Chad J.;Stafforini, Diana M.
以往的研究表明，参与脂质代谢途径的关键酶在正常组织和肿瘤组织中的表达存在差异。然而，脂质代谢酶表达失调和脂质稳态改变在癌变中所起的确切作用仍有待确定。脂肪酸合成酶在多种癌症中过度表达，包括乳腺癌和前列腺癌。本研究的目的是检查在人类乳腺癌和前列腺癌中额外的脂质代谢酶的表达模式。这是通过分析已发表的表达数据库完成的，并通过免疫印迹测定进行确认。我们的研究结果表明，脂肪酸激活酶，长链脂肪酰辅酶A合成酶4（ACSL 4），在人类乳腺癌中的差异表达作为雌激素受体α（ER）状态的函数。在10项单独的研究中，ACSL 4信使RNA（mRNA）在ER阴性乳腺肿瘤中过表达。在检测的50株乳腺癌细胞系中，19株ER阳性细胞系中有17株（89%）ACSL 4 mRNA表达阴性，31株ER阴性细胞系中有20株（65%）表达ACSL 4 mRNA。乳腺癌和前列腺癌中雄激素受体状态也观察到ER表达和ACSL 4表达之间呈负相关。此外，类固醇激素敏感性的丧失，如在Raf 1转染的MCF-7细胞和LNCaP-Al细胞中观察到的，与ACSL 4表达的诱导相关。在MDA-MB-231乳腺癌细胞中消融ACSL 4表达对细胞增殖没有影响;然而，在缺乏ACSL 4的细胞中，对三酸甘油酯C的细胞毒性作用的敏感性增加了三倍。
Previous studies have shown that key enzymes involved in lipid metabolic pathways are differentially expressed in normal compared with tumor tissues. However, the precise role played by dysregulated expression of lipid metabolic enzymes and altered lipid homeostasis in carcinogenesis remains to be established. Fatty acid synthase is over-expressed in a variety of cancers, including breast and prostate. The purpose of the present study was to examine the expression patterns of additional lipid metabolic enzymes in human breast and prostate cancers. This was accomplished by analysis of published expression databases, with confirmation by immunoblot assays. Our results indicate that the fatty acid-activating enzyme, long-chain fatty acyl-CoA synthetase 4 (ACSL4), is differentially expressed in human breast cancer as a function of estrogen receptor alpha (ER) status. In 10 separate studies, ACSL4 messenger RNA (mRNA) was overexpressed in ER-negative breast tumors. Of 50 breast cancer cell lines examined, 17 (89%) of 19 ER-positive lines were negative for ACSL4 mRNA expression and 20 (65%) of 31 ER-negative lines expressed ACSL4 mRNA. The inverse relationship between ER expression and ACSL4 expression was also observed for androgen receptor status in both breast and prostate cancers. Furthermore, loss of steroid hormone sensitivity, such as that observed in Raf1-transfected MCF-7 cells and LNCaP-Al cells, was associated with induction of ACSL4 expression. Ablation of ACSL4 expression in MDA-MB-231 breast cancer cells had no effect on cell proliferation; however, sensitivity to the cytotoxic effects of triacsin C was increased three-fold in the cells lacking ACSL4.