Abstract 1772: Calcium activated nucleotidase 1 (CANT1) promotes progression of prostate carcinomas

Abstract Aims: Previously, we identified Calcium-activated nucleotidase 1 (CANT1) mRNA to be overexpressed in human prostate cancer, however, so far no involvement of CANT1 in the progression of human tumours was reported. Therefore the protein expression level of CANT1 in prostate tumours was determined, followed by the elucidation of a functional implication of CANT1 overexpression in prostate cancer progression. Methods: Two tissue microarrays including 1100 prostate samples from two different institutions were constructed to examine the protein expression level of CANT1. The role of CANT1 in tumour progression was assessed in two prostate cancer cell lines in an RNA interference based approach. Cell number and DNA synthesis rate were determined by in vitro assays to measure cell proliferation, further cell migration was studied in transwell chamber assays. Results: A recurrent overexpression of CANT1 protein in human prostate cancers was confirmed on the tissue microarrays. Functionally, CANT1 knockdown induced a reduction of LNCaP as well as PC-3 cell number, which was caused by a diminished DNA synthesis rate. Moreover, a considerable decrease of cell migration towards a fibronectin gradient was observed in both cell lines upon CANT1 knockdown. This decreased cell mobility was also accompanied by morphological cell changes. Conclusions: Two cellular processes that are directly linked to tumour progression are markedly impaired upon CANT1 knockdown in prostate cancer cell lines, demonstrating for the first time a tumourbiological relevance of CANT1 expression. In future experiments the mechanism how CANT1 exerts its effects on proliferation and migration will be elucidated as well as the pathways that lead to CANT1 overexpression in prostate cancer. This will contribute to a better understanding of prostate carcinogenesis and to the evaluation of the potential of CANT1 as a therapeutic target. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1772.