1998 Fiscal Year Final Research Report Summary
Analysis of genes related to human breast carcinogenesis
| Project/Area Number |
09470521
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | Cancer Institute, Japanese Foundation for Cancer Research |
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Principal Investigator |
MIKI Yoshino Cancer Institute, Japanese Foundation for Cancer Research Dcpt. Molecular Diagonosis, Chief, 癌研究所・遺伝子診断研究部, 部長 (10281594)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Breast cancer / Tumor suppressor gene / H-cadherin / TSG101 / beta-catenin / GSK-38 |
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| Research Abstract |
Prognostic indicators for breast cancer patients are needed to determine grade of malignancy, predict postoperative prognosis, and guide adjuvant therapy.To detect genetic alterations that have potential to be new diagnostic markers, we have performed mutation analysis of candidate genes in sporadic breast cancers.
The H-cadherin gene was localized to 16q24 and its expression was shown to be significantly reduced in breast cancers.Other investigators reported that deletions at 16q24 were correlated with distant metastasis.These data suggest that H-cadherin may be a candidate for the tumor suppressor gene.We examined the H-cadherin gene for mutation in 50 primary breast cancers, and identified no mutations other than 5-bp deletion in a single tumor.The very low frequency of mutation suggests that H-cadherin is usually not a primary target for breast carcinogenesis, and that reduction of its expression is likely to be a consequence of some other genetic events.
The TSG101 was mapped to 11p
… More
15, a region proposed to contain tumor suppressor genes.Intragenic deletions of TSG101 in primary breast carcinomas were reported.We examined TSG101 in 50 primary breast cancers, and no deletion was found.
b-catenin is considered to play an important role as a member in the Wnt signal transduction pathway.In colon cancers b-catenin was shown to have oncogenic activity when it was mutated or when it was up-regulated by dysfunction of APC.GSK3b phosphorylates APC and that phosphorilation enhances the binding of APC to b-catenin.We screened the b-catenin and GSK3b genes for mutations in 50 primary breast cancers, and no mutation in b-catenin was found and a insertion within GSK3b was identified in a single tumor.Furthermore Western blotting analysis of these breast cancers revealed no overexpression of b-catenin.
Although we have not found any novel genes that play an important role in human breast carcinogenesis, it is very important to continue the experiments to screen candidates for mutation in breast cancers. Less
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[Publications] Nomizu, T., Tsuchiya, A., Kanno, M., Katagata, N., Watanabe, F., Yamaki, Y., Abe, R., Miki Y.: "Clinicopathological features of hereditary breast cancxer." Breast Cancer. 4. 239-242 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Emi, M., Matsushima, M., Katagirl, T., Yoshimoto, M., Kasumi, F., Yokota, T., Nakata, T., Miki, Y., Nakamura, Y.: "Multiplex mutation screening of the BRCA1 gene in 1000 Japanese breast cancers." Jpn.J.Cancer Res.89. 12-16 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Katagiri, T., Saito, H., Shinohara, A., Ogawa, H., Kamada, N., Nakamura, Y., Miki, Y.: "Multiple possible sites of BRCA2 interacting with DNA repair protein Rad51" Genes, Chromosomes & Cancer. 21. 217-222 (1998)
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