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Prostaglandin E stimulates progression-related gene expression in early colorectal adenoma cells

Mauritz, I ; Westermayer, S ; Marian, B ; Erlach, N ; Grusch, M ; Holzmann, K

British journal of cancer, 2006-06, Vol.94 (11), p.1718-1725 [Periódico revisado por pares]

England

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Título:
Prostaglandin E stimulates progression-related gene expression in early colorectal adenoma cells
Autor: Mauritz, I ; Westermayer, S ; Marian, B ; Erlach, N ; Grusch, M ; Holzmann, K
Assuntos: Adenoma - genetics ; Cell Line, Tumor ; Colonic Neoplasms - genetics ; Colorectal Neoplasms - genetics ; Cyclooxygenase 2 - genetics ; Dinoprostone - pharmacology ; DNA Primers ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; Polymerase Chain Reaction ; Prostaglandins - metabolism ; Proto-Oncogene Proteins c-jun - metabolism ; Signal Transduction
É parte de: British journal of cancer, 2006-06, Vol.94 (11), p.1718-1725
Descrição: Upregulation of cyclooxygenase-2 (COX-2) and prostaglandin-dependent vascularisation in small adenomatous polyps is an essential part of colon carcinogenesis. To study the underlying cellular mechanisms, LT97 and Caco2 human colorectal tumour cells not expressing endogenous COX-2 were exposed to 1 microM prostaglandin E(2) (PGE(2)) in their medium. At 30 min after addition, expression of c-fos was stimulated 5-fold and 1.3-fold, respectively, depending on the activation of both extracellular signal-regulated kinase and p38. The amount of c-jun in nuclear extracts was increased 20% in LT97 cells. Expression of COX-2 was upregulated 1.7-fold in LT97 cells and 1.5-fold in Caco2 2 h after prostaglandin (PG) addition by a p38-mediated pathway. The known PGE(2) target gene vascular endothelial growth factor (VEGF) was not modulated. Effects of sustained PGE(2) production were studied in VACO235 cells that have high endogenous COX-2 and in LT97 cells infected with an adenovirus expressing COX-2. Prostaglandin E(2) secretion into the medium was 1-2 nM and 250 pM, respectively. Expression of both VEGF and c-fos was high in VACO235 cells. In LT97 cells, COX-2 upregulated c-fos expression and c-jun content in nuclear extracts 1.7- and 1.2-fold, respectively, in a PG-dependent way. This shows that exogenous PGE(2) as well as COX-2 overexpression affect signalling and gene expression in a way that enhances tumour progression.
Editor: England
Idioma: Inglês

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Prostaglandin E stimulates progression-related gene expression in early colorectal adenoma cells

Mauritz, I ; Westermayer, S ; Marian, B ; Erlach, N ; Grusch, M ; Holzmann, K

England

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