Distinct effects of gonadotropin-releasing hormone analogs and 4-hydroxytamoxifen on pS2 mRNA expression with respect to cell proliferation in MCF-7 breast cancer cells.
Gonadotropin-releasing hormone (GnRH) analogs and antiestrogens display direct antiestrogenic effects on the proliferation of hormone-sensitive breast cancer cells. This study aimed to determine whether growth inhibition of 17 beta-estradiol-stimulated MCF-7 breast cancer cells by the agonist D-Trp6 GnRH, the GnRH antagonist BIM 21009C and 4-hydroxy-tamoxifen (OHT) respectively occurred through alterations of the estrogen receptor (ER)-mediated intracellular pathway. The pS2 mRNA expression is primarily dependent on activated ER in MCF-7 cells, and pS2 protein could act as a growth factor. Drug effect on pS2 mRNAs were qualitatively compared to those on the cell cycle. Unlike OHT, GnRH analogs did not suppress the 17 beta-estradiol-induced pS2 mRNA expression whilst the cell cycle was blocked. The pS2 mRNA expression was induced by D-Trp6 GnRH alone without effect on the cell cycle. The outcome of our study is double. Firstly, GnRH analogs are distinct from OHT as regards their effects on the ER-mediated intracellular pathway. Secondly, pS2 mRNA expression is not strictly related to MCF-7 cell proliferation, suggesting that pS2 protein has a function other than that of critical growth regulator.
Neri
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Laboratoire de Cancérologie Expérimentale, Faculté de Médecine Nord, Marseille, France.
Colomb
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Roux-Dosseto
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Martin
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PM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D011506:Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D000071163:Trefoil Factor-1; D017329:Triptorelin Pamoate; D025521:Tumor Suppressor Proteins
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D017329:Triptorelin Pamoate; D013629:Tamoxifen; C016601:afimoxifene; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; C046002:LHRH, (N)-Ac-3(2-naphthyl)Ala(1)-(4-Cl-Phe)(2)-Trp(3)-Arg(6)-Phe(7)-AlaNH2(10)-