CRH produced by human endometrial cells exerts decidualizing activity via an autocrine mechanism mediated via CRH-R1 receptors. We postulated that such activity exerted by CRH on normal endometrial cells might translate into an antiproliferative action on endometrial-derived malignancies, provided that neoplastic cells maintain the expression of CRH receptors. In this light, here we investigated the possible antiproliferative effects of CRH in an adenocarcinoma cell line derived from human endometrium. CRH induces time- and concentration-dependent inhibition of Ishikawa cell growth, the maximal effect (50% inhibition) being achieved after 3 d of treatment with 10(-7) m CRH. A decrease in telomerase activity, which paralleled tumor growth inhibition, was also observed in CRH-treated samples. The antiproliferative effect was confirmed by colony-formation assay for long-term survival. This effect was counteracted in a concentration-dependent manner by both a-helical CRH and astressin; the former also showed intrinsic inhibitory activity. These findings suggested the involvement of CRH-R1 receptor subtype; this hypothesis was confirmed by RNase protection analysis showing the expression of human CRH-R1 mRNA. Experiments with the PKA inhibitor 14-22 amide and forskolin, as well as the measurement of intracellular cAMP, suggested the downstream involvement of cAMP-PKA pathway in CRH-induced inhibition of Ishikawa cell growth.

Graziani G., T.L. (2002). CRH inhibits cell growth of human endometrial adenocarcinoma cells via CRH-receptor 1-mediated activation of cAMP-PKA pathway. ENDOCRINOLOGY, 143(3), 807-813 [10.1210/en.143.3.807].

CRH inhibits cell growth of human endometrial adenocarcinoma cells via CRH-receptor 1-mediated activation of cAMP-PKA pathway

GRAZIANI, GRAZIA;TENTORI, LUCIO;
2002

Abstract

CRH produced by human endometrial cells exerts decidualizing activity via an autocrine mechanism mediated via CRH-R1 receptors. We postulated that such activity exerted by CRH on normal endometrial cells might translate into an antiproliferative action on endometrial-derived malignancies, provided that neoplastic cells maintain the expression of CRH receptors. In this light, here we investigated the possible antiproliferative effects of CRH in an adenocarcinoma cell line derived from human endometrium. CRH induces time- and concentration-dependent inhibition of Ishikawa cell growth, the maximal effect (50% inhibition) being achieved after 3 d of treatment with 10(-7) m CRH. A decrease in telomerase activity, which paralleled tumor growth inhibition, was also observed in CRH-treated samples. The antiproliferative effect was confirmed by colony-formation assay for long-term survival. This effect was counteracted in a concentration-dependent manner by both a-helical CRH and astressin; the former also showed intrinsic inhibitory activity. These findings suggested the involvement of CRH-R1 receptor subtype; this hypothesis was confirmed by RNase protection analysis showing the expression of human CRH-R1 mRNA. Experiments with the PKA inhibitor 14-22 amide and forskolin, as well as the measurement of intracellular cAMP, suggested the downstream involvement of cAMP-PKA pathway in CRH-induced inhibition of Ishikawa cell growth.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14
English
Con Impact Factor ISI
astressin; corticotropin releasing factor; corticotropin releasing factor receptor; corticotropin releasing factor receptor 1; cyclic AMP; cyclic AMP dependent protein kinase; cyclic AMP dependent protein kinase inhibitor; forskolin; messenger RNA; ribonuclease; telomerase; unclassified drug; antineoplastic activity; article; autocrine effect; cancer cell culture; cancer inhibition; cell growth; colony forming unit; controlled study; decidualization; dose time effect relation; drug antagonism; drug effect; drug mechanism; endometrium carcinoma; enzyme activation; enzyme activity; human; human cell; priority journal; protein expression; ribonuclease protection assay; Adenocarcinoma; Cell Division; Corticotropin-Releasing Hormone; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Endometrial Neoplasms; Female; Humans; Nuclease Protection Assays; Receptors, Corticotropin-Releasing Hormone; Signal Transduction; Telomerase; Tumor Cells, Cultured
Graziani G., T.L. (2002). CRH inhibits cell growth of human endometrial adenocarcinoma cells via CRH-receptor 1-mediated activation of cAMP-PKA pathway. ENDOCRINOLOGY, 143(3), 807-813 [10.1210/en.143.3.807].
Graziani, G; Tentori, L; Portarena, I; Barbarino, M; Tringali, G; Pozzoli, G; Navarra, P
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/52206
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