Epigenetic regulation of protein tyrosine phosphatase PTPN12 in triple-negative breast cancer.

Abstract Aims The present study showed that the expression of PTPN12 is epigenetically regulated. 5-Azacytidine (5-Azac), a DNA hypomethylating agent, significantly increased the expression of PTPN12 at low concentrations (1 μM and 2.5 μM) and decreased the expression of PTPN12 at 5 μM in the MDA-MB-231 and BT-549 triple-negative breast cancer cell lines. Main methods Human MCF-7, MDA-MB-231 and BT-549 cells were exposed to different concentrations of 5-Azac for 24 and 48 h. RT-PCR was performed to determine the mRNA expression of PTPN12, E-cadherin and miRNA-124. Western blotting was performed to assess the protein expression of various proteins, including PTPN12, E-cadherin, DNMT and PARP. Key findings 5-Azac, a DNA hypomethylating agent, significantly increased the expression of PTPN12 at low concentrations (1 μM and 2.5 μM) and decreased PTPN12 expression at 5 μM. We provide the first evidence that PTPN12 expression is epigenetically regulated and that it is up-regulated at a lower dose of a DNMT1 inhibitor in MDA-MB-231 and BT-549 cells. Interestingly, the levels of miRNA-124 were increased only at 5 μM, the concentration at which PTPN12 expression was suppressed. Significance To the best of our knowledge, this is the first report that highlights the therapeutic potential of low-dose 5-Azac for the treatment of TNBC. Therefore, 5-Azac, an agent that has already been tested in acute myeloid leukemia, may be more effective at lower doses for the treatment of triple-negative breast cancer.