| Project/Area Number |
63570778
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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 | Osaka University |
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Principal Investigator |
KOMURA Hiroko (1989-1990) Osaka Univ. Med. Sch. Lecturer Dept. OB/GYN, 医学部, 助手 (80195685)
田坂 慶一 (1988) 大阪大学, 医学部, 助手 (50155058)
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| Co-Investigator(Kenkyū-buntansha) |
寺川 直樹 大阪大学, 医学部, 講師 (90135690)
甲村 弘子 大阪大学, 医学部, 助手 (80195685)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1990: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1989: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1988: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Transforming growth factor alpha / Epidermal growth factor / Epidermal growth factor receptor / Northern analysis / Immunocytochemistry / Monolayer cell culture / Autocrine growth mechanism / TGFα / EGF receptor / autocrine growth / nudeマウス / 顎下腺 / sialoadenectomy / 卵巣癌 / EGF受容体 / メッセンジャ-RNA / ノ-ザンブロッティング / 成長因子(grouth factor) / ガン遺伝子(oncogene) / v-erb-B / pE7 / Dot blotting |
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| Research Abstract |
We analyzed 35 cases of primary human ovarian adenocarcinomas for the expression of epidermal growth factor receptor using ^<125>-EGF as a ligand. Twenty out of these 35 cases possessed specific EGF receptor, this was as frequent as 57%. We, next, analyzed the expression of ligands which can bind to EGF receptor by northern blot analysis using transforming growth factor alpha cDNA and prepro-EGF cDNA as probes, and found TGFalpha but not EGF mRNA to be expressed in EGF receptor positive ovarian cancers. Immunocytochemical studies revealed that TGFalpha and EGF receptor protein but not EGF proteins were expressed on the cells from EGF receptor positive cancers. These findings suggested the TGFalpha/EGF receptor autocrine mechanism in these cells. We, therfore, assessed the biological significance of this mechanism on the growth of ovarian cancer cells. As an agonist to this autocrine mechanism TGFalpha was added to the monolayer cell cultures from primary human ovarian cancers and as the antagonists monoclonal antibodies against TGFalpha, EGF and EGF receptor were used. TGFalpha added to the cultured cells from EGF receptor positive cancers promoted the ^3H-thymidine incorporation into cells dose dependently, and more importantly, TGFalpha and EGF receptor monoclonal antibodies reduced cell growth in a dose dependent manner. EGF Ab added to the culture medium did not show any effects on these cells. contrary to these results in EGF receptor positive cells, TGFalpha and monoclonal antibodies against TGFalpha and EGF receptor exhibited no significant effects on the cell growth. All these results strongly suggest that TGFalpha/EGF receptor autocrine growth mechanism is crucial in EGF receptor expressed human ovarian cancers.
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