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Characteristics of metabolism of fatty acid and glucose in human cancer

人类癌症中脂肪酸和葡萄糖的代谢特征

基本信息

批准号：
12670169
负责人：
SUZUKI Toshimitsu
金额：
$ 2.56万
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670169/
关键词：
FATTY ACID SYNTHASE FATTY ACID BINDING PROTEIN GLUCOSE TRANSPORTER HUMAN CARCINOMA SOFT TISSUE SARCOMA METASTATIC MODEL DRUG RESISTENCE CERULENIN 食道軽度異型上皮ヒト食道癌ヒト軟部肉腫ヒト肺癌肝型脂肪酸結合蛋白

项目摘要

1. Fatty acid synthase (FAS) was highly expressed in prenoplastic lesions of esophagus and stomach in addition to their carcioma. Bladder carcinoma exhibited high expression of FAS even in dysphasia and/or carcinoma in situ. On the other hand, FAS expression was not observed in hyperplasia or adenoma of the pancreas in spite of high expression in the pancreatic carcinoma.2. FAS expression combined with Ki-67 labelling indices was an indicator of prognosis in soft tissue sarcoma.3. Cell lines of colon carcinoma and undifferentiated thyroid carcinoma showed necrosis and apoptosis by treatment with cerulenin, a specific inhibitor for FAS, with marked decrease in ATP content in the treated cancer cells.4. Multi-drug resistant leukemic cell lines treated with cerulenin exhibited more pronounced cell death1 than their parent cell lines did.5. The cerulenin-treated cancer cells revealed decreased expression of acyl Co-A synthase, lysophosphatidic acid transferase-β and N-myristoylacyltransferase-2, and increased expression of middle chain acyl-CoA dehydrogenase, lysophosphatidic acid acyltransferase-α and N-mirystoylacyltransferase-1. In addition, the cells disclosed increased expression of hexokinase-1.6. The carcioma cells derived from widely metastatic clone of AH7974 rat ascites hepatoma highly expressed FAS when they migrated in the blood vessels, while the parent cells of AH7974 in the blood vessels were very low or null in FAS-expression.7. Expression of liver type fatty acid binding protein (FABP) showed similar pattern to that of FAS in stomach and lung cancers.8. Expression of heart type FABP was associated with progression, aggressiveness of stomach carcinoma and patient survival of this cancer, which was in marked contrast with breast carcinoma of which growth was suppressed by H-FABP.9. Glucose trasporter-1 was a marker for prognosis of stomach and lung carcinoma.

1.脂肪酸合酶(FAS)在食管癌和胃癌前病变中高表达。膀胱癌即使在语言障碍和/或原位癌中也表现出 FAS 高表达。另一方面，FAS在胰腺癌中高表达，但在胰腺增生或腺瘤中未见表达。 2． FAS表达联合Ki-67标记指数是判断软组织肉瘤预后的指标。 3． FAS特异性抑制剂浅蓝素处理后，结肠癌和未分化甲状腺癌细胞出现坏死和凋亡，处理后的癌细胞中ATP含量明显下降。 4．用浅蓝素处理的多重耐药白血病细胞系比其亲本细胞系表现出更明显的细胞死亡1。5。浅蓝菌素处理的癌细胞显示酰基辅酶A合酶、溶血磷脂酸转移酶-β和N-肉豆蔻酰基转移酶-2的表达降低，而中链酰基辅酶A脱氢酶、溶血磷脂酸酰基转移酶-α和N-肉豆蔻酰基转移酶-1的表达增加。此外，细胞中己糖激酶1.6的表达增加。 AH7974大鼠腹水肝癌广泛转移克隆来源的癌细胞在血管内迁移时FAS高表达，而AH7974在血管内的亲代细胞FAS表达极低或无。7．肝型脂肪酸结合蛋白(FABP)在胃癌和肺癌中的表达与FAS相似。8．心型FABP的表达与胃癌的进展、侵袭性和患者的生存有关，这与H-FABP抑制乳腺癌的生长形成鲜明对比。9。葡萄糖转运蛋白-1是胃癌和肺癌预后的标志物。