| Project/Area Number |
60570583
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | TOKYO MEDICAL AND DENTAL UNIVERSITY |
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Principal Investigator |
MURAYAMA YOICHI TOKYO MEDICAL AND DENTAL UNIVERSITY, 医学部, 助手 (60126258)
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| Co-Investigator(Kenkyū-buntansha) |
AOYAGI KAZUHIKO TOKYO MEDICAL AND DENTAL UNIVERSITY, 医学部, 講師 (90013953)
MISHIMA YOSHIO TOKYO MEDICAL AND DENTAL UNIVERSITY, 医学部, 教授 (00010158)
KURATA SHUNICHI TOKYO MEDICAL AND DENTAL UNIVERSITY, 難治疾患研究所, 助手 (60140901)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | SHBG(Sex hormone binding globulin) / Estrogen / Breast cancer / Oncogene / Epidermal growth factor receptor / Estrogen receptor / Estrogen Receptor / EGF Receptor / 抗エストロージェン / 発癌 |
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| Research Abstract |
We found a novel regulation system of plasma unbound estradiol concentration in normal premenopausal women. Concentration of unbound estradiol which has biological activity was regulated by both plasma total estradiol concentration and SHBG. High binding capacity of SHBG for 17 <beta> -estradiol was associated with high levels of plasma unbound estradiol and the presence of hormone dependent breast cancer. Estradiol activated ras, myc, and fos proto-oncogenes of normal breast cells,and also activated ras, myc, and fos oncogenes of breast cancer cells in primary culture. Estradiol activated RNA activities of EGFR ( Epidermal growth factor receptor) gene and estrogen receptor gene in addition of activation of above three kinds of oncogenes in MCF 7 human breast cancer cells.
On the other hand, anti-estrogen ( Tamoxifen ) suppressed above two kinds of receptor genes, and oncogenes ( ras, myc, and fos oncogenes ). These results indicate that high estradiol binding capacity on SHBG with high levels of unbound estradiol in plasma and cytosol is an important RISK FACTOR and has an important role in the carcinogenesis of human breast cancer.
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