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在具有高频率的人类癌症中表达，其表达与脂肪代谢，马敏感，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）的表达主要与肾上腺敏感的细胞，肾小球，乳腺元素，前态，前敏序列，前态，前态，前态，前态，前态）（皮脂腺腺体。脂肪细胞，肺II型肺泡细胞）成人，而在人胎儿的增殖细胞中发现。 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），胃癌（270/434）和肺癌（127/200）的中间频率（127/200）和软组织肉瘤中的低频（2…更多0/64）。（3）FAS的高表达表明，乳腺癌和乳腺癌的乳腺癌癌症中的乳腺癌和乳腺癌的快速预后较差，但在其他癌症中却不含其他（4）。用雌激素或孕酮处理后的FAS-MRNA。（5）八个胃癌细胞系揭示了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。这些包括酰基-COA结合蛋白，酰基-COA脱氢酶，溶物磷脂酸酰基转移酶-α和-β和N-米尔斯利酰基转移酶。（6）Cerulenin，Fas的特异性抑制剂，一种在take fas takigawa，Take Fas-mrna的人类胃癌细胞线的抑制作用，在48 HOR中，在48 HOR中得到了人类胃癌细胞的生长。与未处理的对照相比，处理细胞中的死细胞在约20％的情况下增加了约20％，但两组之间的凋亡细胞保持不变。（7）cerulenin引起与脂肪酸代谢相关的蛋白质和酶的表达下降，胃癌细胞线中的蛋白质和脂肪酸代谢，尤其是在高硫群中，尤其是在酰基coA coa synthase acrendy acdeyly-coayl-coa基因中，长链蛋白酶酶，蛋白质蛋白质。脱氢酶，溶物磷脂酸酰基转移酶-β和n- myristoil酰基转移酶。较少的