Abstract
Identification of cancer-associated genes is critical for developing effective treatments of colorectal cancer (CRC). A limited number of studies have examined the mechanisms and genes underlying CRC. Abnormal transforming growth factor beta (TGF-?) expression was observed at different stages of carcinoma. We examined the effect of cancer-related cytokine TGF-? on carbonic anhydrase (CA) III gene expression in colon cancer HT-29 cells. TGF-? (500 U/mL) downregulated CAIII gene expression at both the mRNA and protein levels. Transient transfection experiments indicated that different CAIII promoter constructs were active in HT-29 cells. TGF-? reduced transcriptional activity of all promoter constructs, indicating that the potential response element for TGF-?-directed transcription lies within the -108/+86 region of the CAIII promoter. According to the non-Smad pathway inhibitory assay, TGF-? downregulated the CAIII gene through mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphoinositide-3-kinase (PI3K) pathways. The same decreasing effect was determined in the Saos-2, osteosarcoma cell line, indicating that the effect of TGF-? on CAIII was not tissue-specific. However, examination of PI3K and MAPK/ERK signaling pathways with suitable inhibitors revealed that the PI3K but not the MAPK/ERK pathway was responsible for TGF-? downregulation.
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