| Project/Area Number |
12670169
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
SUZUKI Toshimitsu Fukushima Medical University, School of Medicine, Professor, 医学部, 教授 (80018952)
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| Co-Investigator(Kenkyū-buntansha) |
SUGINO Takashi Fukushima Medical University, School of Medicine, assistant, 医学部, 助手 (90171165)
WATANABE Kazuo Fukushima Medical University, University Hospital, associate professor, 医学部, 助教授 (80167105)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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