Expression of fatty acid synthase, and proteins and enzymes related to fatty acid metabolism in human cancer

我们证实FAS在人类癌症中高频表达，其表达与脂肪代谢、激素敏感性、细胞增殖以及参与脂肪酸代谢的蛋白和酶的表达密切相关。(1)脂肪酸合成酶（FAS）主要在激素敏感细胞（肾上腺、乳腺、前列腺、子宫内膜）或脂质代谢高的细胞（皮脂腺）中表达。脂肪细胞，肝II型肺泡细胞)，而在人胎儿的增殖细胞中发现。小脑皮层神经元和篮细胞也有fas表达。(2)人类肿瘤中FAS阳性约占74%（1131例中阳性838例），以乳腺癌（243/243）、膀胱癌（55/64）、食管癌（85/88）、肝细胞癌（38/47）居多，以胃癌（270/434）、肺癌（127/200）居中，以软组织肉瘤(2…(3) FAS在乳腺癌和膀胱癌中高表达预示预后较差，而在其他肿瘤中高表达预后较差。(4)乳腺癌细胞系MCF-7在雌激素或黄体酮处理后FAS-mRNA快速升高。他莫昔芬可消除雌激素的作用。(5) 8株胃癌细胞株均表达fas，其与脂肪酸代谢相关蛋白和酶的表达密切相关。包括酰基辅酶a结合蛋白、酰基辅酶a脱氢酶、溶血磷脂酸酰基转移酶-α和-β、n -肉豆蔻醇酰基转移酶。(6) FAS特异性抑制剂Cerulenin在治疗后48小时内抑制了表达FAS- mrna的人胃癌细胞株TAKIGAWA的细胞生长。与未处理的对照组相比，处理后的细胞死亡细胞增加了约20%，但两组之间的凋亡细胞保持不变。(7) Cerulenin引起胃癌TAKIGAWA细胞系脂肪酸代谢相关蛋白和酶的表达下调，尤其是酰基辅酶a合成酶、超长链酰基辅酶a脱氢酶、长链酰基辅酶a脱氢酶、溶血磷脂酸酰基转移酶-β和n-肉豆醇酰基转移酶的表达下调。少

We confirmed that FAS is expressed in human cancers with high frequency and its expression is closely associated with fat metabolism, hormone-sensitivity, cell proliferation and with expression of protein and enzymes engaged in fatty acid metabolism.(1) Expression of fatty acid synthase (FAS) was mainly detected in hormone-sensitive cells (adrenal, breast, prostate, endometium) or cells with high lipid metabolism (sebaceous glands. fat cells, liver type II alveolar cells of lung) in adult, whereas it was found in proliferating cells of human fetus. Cortical neurons and basket cells of the cerebellum also revealed FAS-expression.(2) Human cancers were positive for FAS at about 74% (838 cases positive among 1131 cases), with high frequency in breast carcinoma (243/243), bladder carcinoma (55/64), esophageal carcinoma (85/88), and hepatocellular carcinoma (38/47), intermediate frequency in gastric carcinoma (270/434) and lung carcinoma (127/200) and low frequency in soft tissue sarcoma (2 … More 0/64).(3) High expression of FAS indicated poor prognosis in breast carcinoma and bladder carcinoma, but not in the others.(4) MCF-7, a breast cancer cell line, showed rapid increase in FAS-mRNA after treatment with estrogen or progesterone. The effect of estrogen was abolished by tamoxifen.(5) Eight gastric cancer cell lines revealed FAS-expression and it was closely linked to the expressions of proteins and enzymes involved in fatty acid metabolism. These include acyl-CoA binding protein, acyl-CoA dehydrogenases, lysophosphatidic acid acyltransferase-α and -β, and N-myristoil acyltransferase.(6) Cerulenin, a specific inhibitor of FAS, arrested cell growth of a human gastric cancer cell line TAKIGAWA, which express FAS-mRNA, within 48 hrs after its treatment. Dead cells increased at about 20% in the treated cells compared with non-treated control but apoptotic cells remained unchanged between both groups.(7) Cerulenin caused down-reguation of expression of proteins and enzymes related to fatty acid metabolism in a gastric cancer cell line TAKIGAWA, especially in acyl-CoA synthase, very long chain acyl-CoA dehydrogenase, long chain acyl-CoA dehydrogenase, lysophosphatidic acid acyltransferase-β and N-myristoil acyltransferase. Less