Abstract 4736: PDE10A overexpression in cancer cells and tumors as compared to normal cells and tissues

Abstract

Abstract Phosphodiesterase 10A (PDE10A) is a cGMP and cAMP degrading PDE isozyme that is expressed in areas of the brain related to motor function and cognition. An elevation in neural PDE10A expression has been strongly linked to many diseases that affect cognition, including schizophrenia and Huntington's disease. Recently, high levels of PDE10A were shown to be expressed in colon tumor cells in vitro and in vivo compared with cells derived from normal colon and normal colonic mucosa (Li et al., Oncogene 2015). PDE10A inhibition by small molecules or genetic silencing, attenuated tumor cell growth by a mechanism involving cGMP/PKG activation, the suppression of β-catenin and a decrease in TCF transcriptional activity (Li et al., Oncogene 2015). These observations suggest that PDE10A may play an important role in tumorigenesis and PDE10A could serve as a novel therapeutic target for colorectal cancer. However, the expression and role of PDE10A in other cancer cell types has yet to be elucidated. Here we report that PDE10A expression is elevated (compared to controls) in tumor cells and solid tumors from xenograft, as well as, genetic models from the colon, breast, and lung using western blot and immunohistochemistry. The human colon adenocarcinoma cell line, HT29, the human breast adenocarcinoma cell line, MDA-MB-231, and the human lung carcinoma cell line, A549, showed elevated expression of PDE10A as compared to the normal colon mucosal epithelial cell line, NCM460, normal human mammary epithelial cells, and normal human airway epithelial cells, respectively. Solid tumors collected from the colons of heterozygous APCmin mice displayed an elevation in PDE10A levels as compared to uninvolved mucosa from the APCmin mice and wild type colon mucosa. Solid tumors collected from the mammary glands of viral transgenic FVB-MMTV-Her2 mice also possessed high levels of PDE10A as compared to FVB wild type mice. These findings suggest that PDE10A could be a novel therapeutic target for not only colorectal cancer, but breast and lung cancers as well. Citation Format: Ashley S. Lindsey, Kevin Lee, Bing Zhu, Ritu Arora, Dennis Otali, Veronica Ramirez-Alacantara, William Grizzle, Gary Piazza. PDE10A overexpression in cancer cells and tumors as compared to normal cells and tissues. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4736.