RESUMEN
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of kidney cancer. This carcinoma is histologically characterized by the presence of clear and abundant cytoplasm. In the present study, we sought to identify genes differentially expressed in ccRCC and build a molecular profile of this cancer. We selected genes described in the literature related to cellular differentiation and proliferation. We analyzed the gene and protein expression by quantitative PCR (qPCR) and immunohistochemistry, respectively, and examined possible epigenetic mechanisms that regulate their expression in ccRCC samples and cell lines. Occludin (OCLN) and growth arrest-specific 1 (GAS1) genes were underexpressed in ccRCC, and we report that miR-122 and miR-34a, respectively, may regulate their expression in this cancer. Furthermore, we showed by qPCR and immunohistochemistry that solute carrier family 2 member 1 (SLC2A1) was significantly overexpressed in ccRCC. The set of genes identified in the present study furthers our understanding of the molecular basis and development of ccRCC.
Asunto(s)
Carcinoma de Células Renales/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias Renales/metabolismo , MicroARNs/genética , Ocludina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Biomarcadores de Tumor , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Proteínas de Ciclo Celular/genética , Proliferación Celular , Inmunoprecipitación de Cromatina , Femenino , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ocludina/genética , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Adulto JovenRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0081937.].
RESUMEN
A melanocyte malignant transformation model was developed in our laboratory, in which different melanoma cell lines were obtained after submitting the non-tumorigenic melanocyte lineage melan-a to sequential cycles of anchorage impediment. Our group has already showed that increased superoxide level leads to global DNA hypermemethylation as well increased Dnmt1 expression few hours after melanocyte anchorage blockade. Here, we showed that Ras/Rac1/ERK signaling pathway is activated in melanocytes submitted to anchorage impediment, regulating superoxide levels, global DNA methylation, and Dnmt1 expression. Interestingly, Ras and Rac1 activation is not related to codon mutations, but instead regulated by superoxide. Moreover, the malignant transformation was drastically compromised when melan-a melanocytes were submitted to sequential cycles of anchorage blockage in the presence of a superoxide scavenger. This aberrant signaling pathway associated with a sustained stressful condition, which might be similar to conditions such as UV radiation and inflammation, seems to be an early step in malignant transformation and to contribute to an epigenetic reprogramming and the melanoma development.