Three amino-acid loop extension (TALE) homeobox proteins MEIS2 is a transcriptional factor that regulates the expression of large sets of downstream target genes by direct binding to their promoter DNA. MEIS2 controls cell growth and differentiation during embryogenesis and carcinogenesis and is overexpressed in ovarian and pancreas cancer. However, the underlying cellular mechanisms remain largely unsolved. In this study, we report that MEIS2 is aberrantly expressed in colorectal adenocarcinoma cells and is profound proliferative and anti-apoptotic effects against colon cancer cells. In immunohistochemical staining, MEIS2 is positively stained in colorectal adenocarcinoma cells and has strong intensity in its nucleus, compared to normal colonic crypt cells. We found that down-regulation of MEIS2 by specific shRNA inhibited the cell growth (50% decrease as compared with control cultures, P<0.001) of HCT-116 colon cancer cell, due to an increase apoptosis (from 3% in control cultures to 65% after 72 hour from transient transfection of MEIS2 shRNA, P<0.001) as determined by MTT and FACScan apoptosis assay. Knockdown of MEIS2 by specific shRNA transfection reduced the expression of Akt, and decreased the phosphorylation of its downstream target proteins such as forkhead transcription factors (FoxO) and p27, and increased the nuclear localization of nonphosphorylated FoxO and p27, which result in activation of apoptosis. In summary, our data indicate that MEIS2 promotes cell growth and plays critical role as novel anti-apoptotic factor through regulation of Akt expression within Akt/PKB signaling pathway in colorectal cancer.

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 1222.