Tumor Suppresser Gene PTEN Was Induced By TSA And X-Ray

The tumor suppressor gene PTEN is a major negative regulator of the PI3K/Akt cellular survival pathway, which has a dual specificity activity: the lipid phosphatase activity and the tyrosine phosphatase activity. It can influences multiple cellular functions including cell growth, survival, proliferation and migration by dephosphorylating a highly acidic peptide substrate and may dephosphorylate protein kinase which is pivotal in many cellular signaling pathways. Overexpression of PTEN increases cell consenescence and induces apoptosis of cancer cells. Histone deacetylase (HDAC) inhibitors such as Trichostatin A (TSA) have emerged as accessory therapeutic agents for multiple human cancers. These HDAC inhibitors can induce transcriptional activation of target genes through reducing HDAC activity and hence affecting acetylation status of core histones. In this study, we treated 293 T cells with TSA or X-ray, examined changes of PTEN and Egr-1 expression by quantitative real-time polymerase chain reaction (RT-PCR). Luciferase reporter assay was used to evaluate the promoter activity of PTEN. We found that the expression of PTEN can be up-regulated by TSA and X-ray. Also histone acetyltransferase p300 was able to synergistically activate PTEN transcription with Egr-1. Moreover TSA can enhance this cooperation. Implies that histone acetylation plays a key role in the regulation of PTEN expression. This study provides further insight into searching a suitable cancer therapeutic method by targeting the tumor suppressor gene PTEN.