Tristetraprolin downregulates the expression of both VEGF and COX-2 in human colon cancer.

Background/aims: Although both VEGF and COX-2 are important factors influencing angiogenesis (and thus, carcinogenesis), the regulation of these factors in carcinogenesis remains poorly understood. The aim is to investigate the effects of tristetraprolin, an AU-rich element-binding protein on the expression of VEGF and COX-2 in human colon cancer cells.

Methodology: Expression of TTP, VEGF and COX-2 in the resected colorectal cancer surgical specimens were analyzed by immunohistochemistry. Colon cancer cells were transfected with luciferase reporter linked to 3'UTR of VEGF or COX-2. The effects of TTP overexpression on the expression of VEGF, COX-2 and luciferase were determined by semiquantitative RT-PCR or luciferase assay.

Results: Immunohistochemical staining of resected colorectal cancer surgical specimens revealed that TTP expression was low in cancer cells but high in non-malignant mucosa. In contrast, the expression of both COX-2 and VEGF was high in cancer cells and very low in non-malignant mucosa. TTP overexpression markedly decreased the expression of both COX-2 and VEGF in colon cancer cells. In addition, TTP inhibited the expression of luciferase linked to 3'UTR of COX-2 or VEGF mRNA.

Conclusions: TTP inhibits the expression of both VEGF and COX-2 and reduced expression of TTP may be responsible for the increased expression of COX-2 and VEGF in human colorectal cancer.