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

我们证实FAS在人类癌症中以高频率表达，并且其表达与脂肪代谢、脂肪敏感性、细胞增殖以及参与脂肪酸代谢的蛋白质和酶的表达密切相关。(1)脂肪酸合成酶（FAS）的表达主要在对脂肪酸敏感的细胞（肾上腺、乳腺、前列腺、子宫内膜）或高脂代谢的细胞（皮脂腺）中检测到。脂肪细胞、肝脏II型肺泡细胞），而在人胎儿的增殖细胞中发现。小脑皮质神经元和篮状细胞也显示FAS表达。(2)人类癌症FAS阳性率约为74% 1131例中838例阳性，以乳腺癌（243/243）、膀胱癌（55/64）、食管癌（85/88）、肝细胞癌（38/47）阳性率高，胃癌（270/434）、肺癌（127/200）为中频率，软组织肉瘤（2 关于我们 0/64）。(3)FAS在乳腺癌和膀胱癌中的高表达提示预后不良，而在其他癌中的表达则无统计学意义。(4)乳腺癌细胞株MCF-7在雌激素或孕激素处理后，FAS-mRNA表达迅速增加。雌激素的作用被三苯氧胺所消除。(5)8株胃癌细胞系表达Fas，Fas表达与脂肪酸代谢相关蛋白和酶的表达密切相关。这些包括酰基辅酶A结合蛋白、酰基辅酶A转移酶、溶血磷脂酸酰基转移酶-α和-β以及N-肉豆蔻酰转移酶。(6)浅蓝菌素是FAS的特异性抑制剂，在其处理后48小时内抑制表达FAS-mRNA的人胃癌细胞系TAKIGAWA的细胞生长。与未处理的对照组相比，处理的细胞中死亡细胞增加约20%，但两组之间的凋亡细胞保持不变。(7)浅蓝菌素可下调胃癌细胞株TAKIGAWA中脂肪酸代谢相关蛋白和酶的表达，尤其是酰基辅酶A合成酶、极长链酰基辅酶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-肉豆蔻酰基转移酶。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