Deregulated Expression of SRC, LYN and CKB Kinases by DNA Methylation and Its Potential Role in Gastric Cancer Invasiveness and Metastasis

Autor(es):Mostrar menos -

Mello, Adriano Azevedo ^[1] ; Leal, Mariana Ferreira ^{[2, 3]} ; Rey, Juan Antonio ^[4] ; Pinto, Giovanny Reboucas ^[5] ; Lamarao, Leticia Martins ^{[6, 7]} ; Montenegro, Raquel Carvalho ^[6] ; Negreiros Nunes Alves, Ana Paula ^[8] ; Assumpcao, Paulo Pimentel ^[9] ; Borges, Barbara do Nascimento ^{[6, 10]} ; Smith, Marilia Cardoso ^[3] ; Burbano, Rommel Rodriguez ^{[6, 9]}

Afiliação do(s) autor(es)

^[1] Univ Fed Campina Grande, Ctr Ciencias Biol & Saude, Campina Grande, PB - Brazil

^[2] Univ Fed Sao Paulo, Dept Ortopedia & Traumatol, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Disciplina Genet, Dept Morfol & Genet, Sao Paulo, SP - Brazil

^[4] Hosp Univ La Paz, Lab Oncogenet Mol, Madrid - Spain

^[5] Univ Fed Piaui, Dept Biomed, Parnaiba, PI - Brazil

^[6] Fed Univ Para, Inst Ciencias Biol, BR-66059 Belem, Para - Brazil

^[7] Fundacao Ctr Hemoterapia & Hematol Para, Lab Testes Acidos Nucleicos, Belem, Para - Brazil

^[8] Univ Fed Ceara, Fac Odontol, Dept Patol Oral, Fortaleza, Ceara - Brazil

^[9] Fed Univ Para, Hosp Univ Joao de Barros Barreto, Nucleo Pesquisa Oncol, BR-66059 Belem, Para - Brazil

^[10] Univ Fed Rural Amazonia, Inst Socioambiental & Recursos Hidr, Ctr Tecnol Agr, Belem, Para - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 10 OCT 13 2015.
• Citações Web of Science: 12

Resumo

Kinases are downstream modulators and effectors of several cellular signaling cascades and play key roles in the development of neoplastic disease. In this study, we aimed to evaluate SRC, LYN and CKB protein and mRNA expression, as well as their promoter methylation, in gastric cancer. We found elevated expression of SRC and LYN kinase mRNA and protein but decreased levels of CKB kinase, alterations that may have a role in the invasiveness and metastasis of gastric tumors. Expression of the three studied kinases was also associated with MYC oncogene expression, a possible biomarker for gastric cancer. To understand the mechanisms that regulate the expression of these genes, we evaluated the DNA promoter methylation of the three kinases. We found that reduced SRC and LYN methylation and increased CKB methylation was associated with gastric cancer. The reduced SRC and LYN methylation was associated with increased levels of mRNA and protein expression, suggesting that DNA methylation is involved in regulating the expression of these kinases. Conversely, reduced CKB methylation was observed in samples with reduced mRNA and protein expression, suggesting CKB expression was found to be only partly regulated by DNA methylation. Additionally, we found that alterations in the DNA methylation pattern of the three studied kinases were also associated with the gastric cancer onset, advanced gastric cancer, deeper tumor invasion and the presence of metastasis. Therefore, SRC, LYN and CKB expression or DNA methylation could be useful markers for predicting tumor progression and targeting in anti-cancer strategies. (AU)

• Processo FAPESP: 09/07145-9 - Aspectos genéticos e epigenéticos na carcinogênese gástrica
• Beneficiário: Marilia de Arruda Cardoso Smith
• Modalidade de apoio: Auxílio à Pesquisa - Temático