Downregulation of DCC sensitizes multiple myeloma cells to bortezomib treatment

Autor(es)

Rodrigues-Junior, Dorival Mendes ^[1] ; Biassi, Thais Priscila ^[1] ; De Albuquerque, Gabriela Estrela ^[1] ; Carlin, Viviane ^[1] ; Buri, Marcus Vinicius ^[2] ; Machado-Junior, Joel ^[1] ; Vettore, Andre Luiz ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, UNIFESP, Lab Biol Mol Canc, Dept Biol Sci, Campus Diadema, Rua Pedro Toledo, 669-11 Andar, BR-04039032 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Insitute Pharmacol, Dept Biochem, Campus Sao Paulo, BR-04044020 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR MEDICINE REPORTS; v. 19, n. 6, p. 5023-5029, JUN 2019.
• Citações Web of Science: 0

Resumo

Multiple myeloma (MM) is an incurable disease; a better understanding of the molecular aspects of this hematological malignancy could contribute to the development of new treatment strategies and help to improve the survival rates of patients with MM. Previously, the methylation status of the deleted in colorectal cancer (DCC) gene was correlated with the survival rate of patients with MM, thus the main goal of this study was to understand DCC contribution to MM tumorigenesis, and to assess the impact of DCC inhibition in the MM response to treatment with bortezomib. Our results demonstrated that hypermethylation of the DCC promoter inhibits gene expression, and DCC silencing is significantly correlated with a reduction in cell viability and an increase in cell death induced by bortezomib. In conclusion, our results suggested that hypermethylation is an important mechanism of DCC expression regulation in MM and that the absence of DCC contributes to the enhanced sensitivity to treatment with bortezomib. (AU)

• Processo FAPESP: 12/01597-8 - ESTUDO FUNCIONAL DOS GENES DCC e TGFBR2 EM LINHAGENS CELULARES DE MIELOMA MULTIPLO
• Beneficiário: Dorival Mendes Rodrigues Junior
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 12/14837-7 - Avaliação do perfil de expressão de microRNAs como marcador diagnóstico de metástases cervicais em pacientes com carcinoma epidermóide de cabeça e pescoço
• Beneficiário: André Lopes Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/20218-2 - Identificação de antíginos câncer-testículo expressos em glioblastomas
• Beneficiário: Karina Ramalho Bortoluci
• Modalidade de apoio: Auxílio à Pesquisa - Regular