Gene expression profile of renal cell carcinomas after neoadjuvant treatment with sunitinib: new pathways revealed

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art_DZIK_Gene_expression_profile_of_renal_cell_carcinomas_after_2017.PDF (338.17 KB)
Citações na Scopus
1
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
WICHTIG PUBLISHING
Autores
Citação
INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS, v.32, n.2, p.E210-E217, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: In renal cell carcinoma (RCC) of the clear cell type, inactivity of the VHL gene induces overexpression of HIF1 alpha and its targets, the tyrosine kinase receptors, promoting RCC development and progression. The discovery of tyrosine kinase inhibitors (TKIs) changed the treatment of these tumors. Other molecular pathways involved in the TKI mechanisms of action have not been described in the literature. The aim of our study was to elucidate alternative mechanisms of action of sunitinib in tumor tissue after neoadjuvant treatment of RCC. Methods: The gene expression profile was accessed using microarray (Affymetrix Human Genome U133 Plus 2.0 platform) and frozen RCC tissues collected from 5 patients with locally advanced non-metastatic tumors who underwent nephrectomy after being treated with 2 cycles of neoadjuvant sunitinib. The results were compared with matched controls comprising 6 patients with no neoadjuvant intervention. Results: There was underexpression of the majority of genes after sunitinib treatment. The lower expression levels of IGFBP1, CCL20, CXCL6 and FGB were confirmed by qRT-PCR in all cases. The downregulation of gene expression leads us to search for methylation as a mechanism of action of the TKI. IGFBP1 was shown to be methylated by methylation-sensitive high-resolution melting technique. Conclusions: The ultimate genetic effects of sunitinib may explain its actions as an antitumor drug that apparently suppresses the expression of important genes related to cell survival, adhesion, invasion and immunomodulation. The methylation of gene promoters was shown to be part of the mechanism of action of this class of drugs.
Palavras-chave
Gene expression, Mechanism of action, Methylation, Renal cell carcinoma, Sunitinib, Tyrosine kinase inhibitor
URI
https://observatorio.fm.usp.br/handle/OPI/19906
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCG
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/55
Artigos e Materiais de Revistas Científicas - LIM/60
Artigos e Materiais de Revistas Científicas - ODS/03