1992 Fiscal Year Final Research Report Summary
Growth inhibition of endometrial cancer cells by aromatase inhibitor and its inhibitory mechanism
| Project/Area Number |
02670752
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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 |
Obstetrics and gynecology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
YAMAMOTO Takara Kyoto Prefect. Univ. Med., OB/GYN Associate Professor, 医学部, 講師 (60158285)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Uterine endometrial cancer cells / Aromatase / Aromatase inhibitor / Sex steroid receptor / DNA synthesis / Uterine adenomyosis |
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| Research Abstract |
Aromatase (estrogen biosynthetase) activity in uterine endometrial cancer tissue is significantly higher than normal endometrial tissues and the aromatase activity is closely related to cancer development. It was examined whether or not human placental aromatase suicide inhibitors (14 alpha-hydroxyandrostenedione: 14 alpha-OHA, 5 alpha-dihydroxynorethindrone : 5 alpha-DHNET) suppress the aromatase activity and the cell proliferation of uterine endometrial cancer. The following results were obtained : (1) 14 alpha-OHA and 5 alpha-DHNET significantly inhibited aromatase activity of uterine tumor tissues (endometrial cancer, uterine leiomyoma and uterine adenomyosis). (2) 14 alpha-OHA and 5 alpha-DHNET did not affect the activities of cholesterol-side chain cleavage enzyme, 11-hydroxylase and 21-hydroxylase in bovine tissue preparations. (3) 14 alpha-OHA itself was not aromatized to 14 alpha-OHE, and 14 alpha-OHE_2, in human placental microsomes. (5 alpha-DHNET is not aromatized from the
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view of its steroid chemical structure). (4) 14 alpha-OHA and 5 alpha-DHNET had almost no binding affinity to estrogen receptor, progestogen receptor or androgen receptor which was prepared from immatured female rabbit uterus. (5) We also examined the effect of testosterone (T) on aromatase activity and tritiated thymidine uptake (DNA synthesis) in various cultured cervical or corpus endometrial cancer cell lines (OMC-4, HHUA, Ishikawa, HEC-59). The results demonstrated that only the HEC-59 cell line had high aromatase activity and increased its DNA synthesis in response to T. This increase of DNA synthesis by T was not suppressed by simultaneous addition of cyproterone acetate, but was by tamoxifen. Thus, the aromatase in cancer cells may contribute partially to cell proliferation if androgen substrate is provided. Also, the increase of DNA synthesis by T in HEC-59 cells was suppressed by simultaneous addition of 14 alpha-OHA.(6) Aromatase was immunohistochemically detected in glandular cells of ectopic and ectopic endometrial tissues. Thus, estrogen is synthesized in the ectopic and ectopic endometrial tissues of women with uterine adenomyosis. Less
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