TGF-β downregulates CAIII expression via MAPK and PI3K signaling pathways in colon carcinoma and osteosarcoma cells
Keywords:CAIII, TGF-β, transcriptional regulation, colon carcinoma, osteosarcoma
- Anormal TGF-β expression is observed at different stages of colon carcinoma. Carbonic anhydrase III (CAIII) is involved in acute myeloid leukemia and hepatic carcinoma.
- TGF-β downregulated CAIII gene expression at the level of mRNA and protein in HT-29 colon cancer cells. TGF-β reduced the transcriptional activity of all CAIII promoter constructs, indicating that the potential response element for TGF-β-directed transcription factor is present within the -108/+86 region of the CAIII promoter. The same decreasing effect was observed in the Saos-2 osteosarcoma cell line.
- Our results show that the effect of TGF-β on CAIII is not tissue-specific.
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-β) expression was observed at different stages of carcinoma. We examined the effect of cancer-related cytokine TGF-β on carbonic anhydrase (CA) III gene expression in colon cancer HT-29 cells. TGF-β (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-β reduced transcriptional activity of all promoter constructs, indicating that the potential response element for TGF-β-directed transcription lies within the -108/+86 region of the CAIII promoter. According to the non-Smad pathway inhibitory assay, TGF-β 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-β 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-β downregulation.
Received: October 8, 2018; Revised: February 26, 2019; Accepted: February 27, 2019; Published online: March 25, 2019
How to cite this article: Aydogan Turkoglu S, Okuyan D, Kockar K. TGF-β
downregulates CAIII expression via MAPK and PI3K signaling pathways in colon carcinoma and osteosarcoma cells. Arch Biol Sci. 2019;71(3):393-401.
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