MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer

Página do item simplificado
dc.contributor.authorCalcagno, Danielle Queiroz [UNIFESP]
dc.contributor.authorFreitas, Vanessa Morais
dc.contributor.authorLeal, Mariana Ferreira [UNIFESP]
dc.contributor.authorSouza, Carolina Rosal Teixeira de
dc.contributor.authorDemachki, Samia
dc.contributor.authorMontenegro, Raquel
dc.contributor.authorAssumpcao, Paulo Pimentel
dc.contributor.authorKhayat, Andre Salim
dc.contributor.authorSmith, Marilia de Arruda Cardoso [UNIFESP]
dc.contributor.authorSantos, Andrea Kely Campos Ribeiro dos
dc.contributor.authorBurbano, Rommel Rodriguez
dc.contributor.institutionFed Univ Para
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T14:34:26Z
dc.date.available2016-01-24T14:34:26Z
dc.date.issued2013-09-23
dc.description.abstractBackground: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation.Methods: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines.Results: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. in vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells.Conclusion: in conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.en
dc.description.affiliationFed Univ Para, Inst Ciencias Biol, Lab Citogenet Humana, BR-66059 Belem, Para, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Morfol & Genet, Disciplina Genet, BR-04023900 São Paulo, SP, Brazil
dc.description.affiliationUniv São Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, São Paulo, SP, Brazil
dc.description.affiliationFed Univ Para, Hosp Univ Joao Barros Barreto, Fac Med, Lab Imunoistoquim,Serv Anat Patol, BR-66059 Belem, PA, Brazil
dc.description.affiliationFed Univ Para, Hosp Univ Joao Barros Barreto, Serv Cirurgia, BR-66059 Belem, PA, Brazil
dc.description.affiliationFed Univ Para, Inst Ciencias Biol, Lab Genet Humana, BR-66059 Belem, PA, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Morfol & Genet, Disciplina Genet, BR-04023900 São Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent10
dc.identifierhttp://dx.doi.org/10.1186/1471-230X-13-141
dc.identifier.citationBmc Gastroenterology. London: Biomed Central Ltd, v. 13, 10 p., 2013.
dc.identifier.doi10.1186/1471-230X-13-141
dc.identifier.fileWOS000325805400001.pdf
dc.identifier.issn1471-230X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/36764
dc.identifier.wosWOS:000325805400001
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofBmc Gastroenterology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGastric canceren
dc.subjectMYCen
dc.subjectFBXW7en
dc.subjectTP53en
dc.titleMYC, FBXW7 and TP53 copy number variation and expression in Gastric Canceren
dc.typeinfo:eu-repo/semantics/article
Arquivos
Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
WOS000325805400001.pdf
Tamanho:
1.16 MB
Formato:
Adobe Portable Document Format
Descrição:
Baixar
Coleções
Em verificação - Geral