title: Osteopontin splice variants expression is involved on docetaxel resistance in PC3 prostate cancer cells.
abstract: Osteopontin (OPN) is a phosphoprotein that activates several aspects of tumor progression. Alternative splicing of the OPN primary transcript generates three splicing isoforms, OPNa, OPNb and OPNc. In this report, we investigated some cellular mechanisms by which OPN splice variants could mediate PC3 prostate cancer (PCa) cell survival and growth in response to docetaxel (DXT)-induced cell death. Cell survival before and after DXT treatment was analyzed by phase-contrast microscopy and crystal-violet staining assays. Quantitative real-time PCR and immunocytochemical staining assays were used to evaluate the putative involvement of epithelial-mesenchymal transition (EMT) and OPN isoforms on mediating PC3 cell survival. Upon DXT treatment, PC3 cells overexpressing OPNb or OPNc isoforms showed higher cell densities, compared to cells overexpressing OPNa and controls. Notably, cells overexpressing OPNb or OPNc isoforms showed a downregulated pattern of EMT epithelial cell markers, while mesenchymal markers were mostly upregulated in these experimental conditions. We concluded that OPNc or OPNb overexpression in PC3 cells can mediate resistance and cell survival features in response to DXT-induced cell death. Our data also provide evidence the EMT program could be one of the molecular mechanisms mediating survival in OPNb- or OPNc-overexpressing cells in response to DXT treatment. These data could further contribute to a better understanding of the mechanisms by which PCa cells acquire resistance to DXT treatment.
authors.affiliation: Programa de Pós Graduação em Ciências Morfológicas, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: K D M
authors.initials: KD
authors.lastname: Nakamura
authors.affiliation: Programa de Pós Graduação Stricto Sensu em Oncologia, Coordenação Geral Técnico Científica do Instituto Nacional de Câncer (INCa), Rio de Janeiro, RJ, Brazil.
authors.forename: T M
authors.initials: TM
authors.lastname: Tilli
authors.affiliation: Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Macaé, RJ, Brazil.
authors.forename: J L
authors.initials: JL
authors.lastname: Wanderley
authors.affiliation: Programa de Pós Graduação em Ciências Morfológicas, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Programa de Pós Graduação em Ciências Morfológicas, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: R M
authors.initials: RM
authors.lastname: Mattos
authors.affiliation: Laboratório de Hemato-Oncologia Celular e Molecular. Programa de Pesquisa em Hemato-Oncologia Molecular-CGTC, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Ferreira
authors.affiliation: Laboratório de Hemato-Oncologia Celular e Molecular. Programa de Pesquisa em Hemato-Oncologia Molecular-CGTC, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil.
authors.forename: C E
authors.initials: CE
authors.lastname: Klumb
authors.affiliation: Programa de Pós Graduação em Ciências Morfológicas, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: L E
authors.initials: LE
authors.lastname: Nasciutti
authors.affiliation: Programa de Pós Graduação Stricto Sensu em Oncologia, Coordenação Geral Técnico Científica do Instituto Nacional de Câncer (INCa), Rio de Janeiro, RJ, Brazil. etelgimba@id.uff.br.|Departamento de Ciências da Natureza (RCN), Instituto de Humanidades e Sáude IHS, Universidade Federal Fluminense, Rua Recife s/n-Bairro Bela Vista, Rio das Ostras, Rio de Janeiro, RJ, 28895-532, Brazil. etelgimba@id.uff.br.
authors.forename: E R
authors.initials: ER
authors.lastname: Gimba
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D000077143:Docetaxel; D015536:Down-Regulation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006801:Humans; D008297:Male; D053495:Osteopontin / Q000235:genetics*; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D043823:Taxoids / Q000494:pharmacology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D043823:Taxoids; D053495:Osteopontin; D000077143:Docetaxel
keywords: Cell survival; Docetaxel; Osteopontin; Prostate cancer; Splicing isoforms