The-1195G Allele Increases the Transcriptional Activity of Cyclooxygenase-2 Gene (COX-2) in Colon Cancer Cell Lines

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

Carina Pereira (Autor) Outra; Hugo Sousa (Autor) Outra; Joana Silva (Autor) Outra; Carla Brandao (Autor) Outra; Claudio Elgueta Karstegl (Autor) Outra; Paul J Farrell (Autor) Outra; Rui Medeiros (Autor) ICBAS; Mario Dinis Ribeiro (Autor) FMUP

Revista

Título: Molecular Carcinogenesis

Vol. 53

Páginas: E92-E95

ISSN: 0899-1987

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 11 Citações

Scopus - 12 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina clínica

Outras Informações

ID Authenticus: P-008-Q22

DOI: 10.1002/mc.22049

Abstract (EN): Up-regulation of cyclooxygenase-2 (COX-2) is an early and key event in human colorectal carcinogenesis (CRC). Nevertheless, the molecular mechanisms leading to this over-expression are largely unknown. We previously reported an association between the -1195G allele and higher predisposition for CRC in a Caucasian population. The biological explanation for the involvement of this polymorphism in CRC remains elusive. We aimed to functionally characterize the influence of the -1195A>G promoter region polymorphism on COX-2 transcription activity in colon cancer cell lines. Luciferase reporter assays were performed to assess whether the -1195A/G alleles influenced COX-2 transcription. The COX-2 promoter's region containing either the -1195A or -1195G alleles was cloned into pGL3-basic reporter vector. The reporter vectors were transiently co-transfected with the pGL4.73 control plasmid to HCT-116 and HCA-7 colon cancer cell lines. The levels of reporter gene expression driven by the -1195G allele-containing COX-2 promoter were significantly higher in both colon cancer cell lines. A 2.2-fold increase in promoter activity was observed in the HCT-116 cell line (P<0.001), and this over-expression was even more noticeable in the HCA-7 COX-2 expressing cell line with a threefold higher transcriptional activity (P=0.001). The -1195G allele appeared to enhance COX-2 transcription, providing a molecular basis underlying the increased susceptibility for CRC and potentially a new mechanism for COX-2 overexpression. (c) 2013 Wiley Periodicals, Inc.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 4