| Project/Area Number |
61570796
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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 | Kobe University School of Medicine |
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Principal Investigator |
MARUO Takeshi Kobe University School of Medicine,Assistane Professor, 医学部附属病院産科婦人科, 講師 (60135811)
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| Co-Investigator(Kenkyū-buntansha) |
KATAYAMA Kazuaki Kobe University School of Medicine,Research associate, 医学部附属病院, 助手 (70112084)
HOSHINA Makoto Kobe University School of Medicine,Research associate, 医学部, 助手 (30116248)
MOCHIZUKI Matsuto Kobe University School of Medicine,Professor, 医学部, 教授 (80030922)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1988: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1987: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Tropko blaso / choriocarcinoma / cervical cancer / hCG / EGF / cyclic AMP / A-kinase / C-kinase / 胎盤 / 絨毛性ゴナドトロピン、腫瘍関連拡原 / TA-4Euideral growth factor(EGF) / PDGF / Cyclic AMP / 繊毛癌 / 繊毛性ゴナドトロピン / TA-4 / Epidermal Growth Factor(EGF) / トロホブラスト / 子宮頸部扁平上皮癌 / プロゲステロン / Epidermal Grouth Factor(EGF) / dibutyryl cAMP / EGF receptor / myc oncogene product |
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| Research Abstract |
The regulation of hCG ( , ) mRNA levels and secretion in normal and malignant trophoblasts was investigated by culturing trophoblastic tissues from normal placenta and choriocarcinoma as well as BeWo cells in the presence or absence of steroid hormone, EGF, PDGF, thyroid hormone or dibutyryl cAMP (dbcAMP). Cellular levels of hCG( , ) and hPL mRNAs were quantitatively estimated by mean grain counts on tissue sections hybridized in situ with labeled cDNA probes. Addition of progesterone (5-20 g/ml) to the culture of normal early placenta caused a decrease in the cellular levels of hCG ( , ) mRNAs and a decline in hCG ( , ) secretion, while progesterone did not affect hPL mNAa levels. Addition of 17 -estradiol (1-10 ng/ml) caused an increase in the cellular levels of hCG mRNA together with an increase in hCG secretion without affecting hCG and hPL mRNA levels. In contrast to normal placenta, choriocarcinoma did not respond to the addition of progesterone. This suggests that progesterone selectively suppresses hCG ( , ) synthesis by normal placenta and that the inhibitory regulation of hCG synthesis in choriocarcinoma is different from that in normal placenta.
On the other hand, addition of EGF (100ng/ml), PDGF (2 U/ml), L-T_3(10 ^<-8>M) or dbcAMP (1mM) caused significant increases in hCG ( , ) levels in cultures of normal placenta as well as BeWo cell line. This suggests that there are no differences in the stimulatory regulation of hCG synthesis between normal and malignant trophoblasts. However, the magnitude of the stimulatory effects of EGF and DbcAMP on hCG synthesis was much greater in BeWo cells than that in normal trophoblastic tissues. EGF-receptor was localized on syncytiotrophoblast. A tumor promotor, phorbol myristate acetate (PMA), which is a stimulator of protein kinase C, synergistically enhanced cAMP-induced stimulation of hCG synthesis and secretion by BeWo cells.
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