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

脂肪酸合成酶以及与脂肪酸代谢相关的蛋白质和酶在人类癌症中的表达

基本信息

批准号：
10670168
负责人：
SUZUKI Toshimitsu
金额：
$ 2.11万
依托单位：
Fukushima Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

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

我们证实FAS在人类癌症中高频率表达，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质和酶的表达密切相关。（1）脂肪酸合酶的表达（ FAS）在成人中主要存在于激素敏感细胞（肾上腺、乳腺、前列腺、子宫内膜）或脂质代谢高的细胞（皮脂腺、脂肪细胞、肝II型肺泡细胞）中，而在人类胎儿的皮质神经元和小脑篮状细胞的增殖细胞也显示有FAS表达。(2)人类癌症中FAS阳性率约为74%(1131例中838例阳性)，其中在乳腺癌中出现频率较高(243例)。 /243)、膀胱癌(55/64)、食管癌(85/88)、肝细胞癌(38/47)，中频在胃癌 (270/434) 和肺癌 (127/200) 中出现频率较低，在软组织肉瘤中出现频率较低 (2 … 更多 0/64)。 (3) FAS 高表达表明乳腺癌和膀胱癌预后较差，但在软组织肉瘤中出现频率较低 (2 … More 0/64)。 (4)乳腺癌细胞系MCF-7在用雌激素或孕激素处理后，FAS-mRNA迅速增加。雌激素的作用被雌激素或黄体酮消除。 (5)八个胃癌细胞系显示FAS表达，并且与参与脂肪酸代谢的蛋白质和酶的表达密切相关，这些蛋白质和酶包括酰基辅酶A结合蛋白、酰基辅酶A脱氢酶、溶血磷脂酸酰基转移酶-α。 (6) FAS 特异性抑制剂 Cerulenin 抑制人胃细胞生长表达 FAS-mRNA 的 TAKIGAWA 癌细胞系在处理后 48 小时内，与未处理的对照相比，细胞中的死亡细胞增加了约 20%，但两组之间的凋亡细胞保持不变。 (7) Cerulenin 导致 -胃癌细胞系 TAKIGAWA 中与脂肪酸代谢相关的蛋白质和酶表达的调节，特别是酰基辅酶 A 合酶、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-肉豆蔻油酰基转移酶较少。