Regulation of estrogen target genes and growth by selective estrogen-receptor modulators in endometrial cancer cells

Página do item simplificado
dc.contributor.authorDardes, Rita de Cássia de Maio [UNIFESP]
dc.contributor.authorSchafer, J. M.
dc.contributor.authorPearce, S. T.
dc.contributor.authorOsipo, C.
dc.contributor.authorChen, B.
dc.contributor.authorJordan, V. C.
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionNorthwestern Univ
dc.date.accessioned2016-01-24T12:33:24Z
dc.date.available2016-01-24T12:33:24Z
dc.date.issued2002-06-01
dc.description.abstractObjective. Tamoxifen has mixed agonist/antagonist activities, leading to tissue-specific estrogen-like actions and endometrial cancer. the purpose of this study was to evaluate the effects of antiestrogens on the growth of estrogen receptor (ER)-positive ECC-1 endometrial cancer cells in vitro and in vivo.Methods. We performed growth studies and luciferase assays using ERE-tK and AP-1 reporters. ERalpha protein expression was measured by Western blot after antiestrogen treatments. We investigated the actions of antiestrogens on the transcription of the pS2 gene in situ measured by Northern blot and the actions of antiestrogens on the VEGF protein secreted by ELISA. ERa, ERbeta, EGFR, and HER2/neu mRNAs were determined by RTPCR. Last, ECC-1 tumors were developed by inoculation of cells into ovariectomized athymic mice and treated with estradiol (EA tamoxifen, raloxifene, and a combination.Results. E-2 induced cell proliferation while antiestrogens did not. E2 and raloxifene down regulated ERa protein; in contrast, 4OHT did not. IC1182,780 completely degraded the receptor. ECC-1 cells express ER,6 at insignificant levels. Luciferase assays did not show any induction in ERE- nor AP-1-mediated transcription by antiestrogens. E2 caused a concentration-dependent increase in pS2 mRNA but antiestrogens did not. E, increased VEGF expression in a dose-dependent manner and antiestrogens blocked E2 action. E. down regulated HER2/neu while 40HT and raloxifene did not change HER2/neu levels compared to control. in addition, EGFR mRNA was down regulated by E, but raloxifene did not change it. Tamoxifen and raloxifene did not promote tumor growth in vivo. However, raloxifene (1.5 mg daily) only partially blocked E-stimulated growth.Conclusions. Tamoxifen and raloxifene are anti proliferative agents and antiestrogens in ECC-1 endometrial cells in vitro and in vivo. the observation that selective estrogen-receptor modulators do not down regulate EGFR and HER2/neu mRNA may provide a potential role for these oncogenes in the development of raloxifene- or tamoxifen-stimulated endometrial cancer. the ECC-1 cell line could provide important new clues about the evolution of drug resistance to tamoxifen and raloxifene. (C) 2002 Elsevier Science (USA).en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Gynecol, São Paulo, Brazil
dc.description.affiliationNorthwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Gynecol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent498-506
dc.identifierhttp://dx.doi.org/10.1006/gyno.2002.6659
dc.identifier.citationGynecologic Oncology. San Diego: Academic Press Inc Elsevier Science, v. 85, n. 3, p. 498-506, 2002.
dc.identifier.doi10.1006/gyno.2002.6659
dc.identifier.issn0090-8258
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/26878
dc.identifier.wosWOS:000176091200018
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofGynecologic Oncology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjecttamoxifenen
dc.subjectraloxifeneen
dc.subjectendometrial canceren
dc.subjectECC-1 cellsen
dc.subjectathymic miceen
dc.titleRegulation of estrogen target genes and growth by selective estrogen-receptor modulators in endometrial cancer cellsen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
EPM - Artigos