Protein Phosphatase 1 regulatory subunits (PPP1R) are a family of small molecules which modify the function and protein targeting of protein phosphatase-1 upon their interactions. Deregulated expression of PPP1R members could often be found in cancer cells. For example, ASPP family is well known for its necessity of p53 function while ASPP silencing leads to carcinogenesis or poor prognosis in cancer patients. Here, one of the PPP1R members (TUSC7) was identified which its role in tumor suppression had been investigated

Using semi-quantitative RT-PCR, expression profile of TUSC7 in cancer cell lines was obtained. TUSC7 was frequently silenced in cancer cells. Bisulfite treated tumor DNA was subjected to Methylation-specific PCR (MSP) using primers flanking across the ∼130bp CpG island of the TUSC7 promoter. It was revealed that silencing of TUSC7 was due to promoter hypermethylation in most of the corresponding cancer cell lines which had been further confirmed by bisulfite genomic sequencing (BGS). Treatment with azacytidine and trichostatin restored TUSC7 expression through demethylating the hypermethylated promoter. To quantitatively determine the extensiveness of cancer cell growth inhibition by TUSC7, colony formation assay was used. It was found that ectopic expression of TUSC7 could inhibit the proliferation of tumor cells, Caski (cervical carcinoma), HCT116 (colon carcinoma) and KYSE150 (esophageal squamaus carcinoma cells) by 40-50%. In addition, ectopic expression of TUSC7 increased the amount of phosphorylated GSK-3beta (pSer9-GSK-3beta) as shown in the western blot analysis. pSer-9 GSK-3beta is the inactive form of GSK-3beta. It has been reported that inactive GSK-3beta may affect p53 activities. To summarize, TUSC7 was found to be a tumor suppressor frequently silenced in cancer cells through epigenetic mechanism. TUSC7 may be significant in regulating the activity of GSK-3beta whose signaling is important in carcinogenesis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 195.