Mirk/Dyrk1b Modulates The Development Of Chemoresistance In Human Ovarian Cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Ovarian cancer is one of the leading causes of cancer death in women and chemoresistance is a major obstacle that need to be overcome in the treatment of ovarian cancer patients. Our previous study along with others have found that the serine/threonine kinase Mirk/Dyrk1B is overexpressed in a wide spectrum of cell lines and clinical specimens of ovarian cancer. It has been known that Mirk/Dyrk1B regulates cell survival and sensitivity to conventional chemotherapeutics, and it also contributes to G0 arrest by destabilization of cyclin D1 and stabilization of p27kip1in ovarian cancer cells. We therefore hypothesize that Mirk/Dyrk1B may be associated with cancer ‘stem cell-like’ sustaining cells and chemoresistance formation. In this study, the mRNA and protein expressions of Mirk/Dyrk1B and the side population (SP) cells in the human ovarian cancer SKOV3, OVCAR5, and A2780S cells were measured during cisplatin resistance development. In addition, the protein expressions of ALDH1, Nanog, Ki-67, and Mirk/Dyrk1B were examined in the clinical specimens obtained from the patients with high-grade serous ovarian cancer before and after neoadjuvant chemotherapy, respectively. It was found that drug resistance formation was accompanied by a significant increase in the mRNA and protein expressions of Mirk/Dyrk1B as well as proportion of SP cells in all ovarian cancer cell strains, which was annulled after knockdown of Mirk/Dyrk1B by shRNA. Moreover, the protein expressions of ALDH1, Nanog, and Mirk/Dyrk1B were up-regulated and ki-67 was down-regulated in the specimens after neodajuvant chemotherapy. Our result confirms the important contribution of Mirk/Dyrk1B-dependent mechanisms into the development of chemoresistance of human ovarian cancer. Citation Format: Jingchun Gao, Ji Li, Heli Gao, Jianxin Tian, Yunyi Lv, Zhihai Yang, Qiuping Zhang, Fandou Kong, Jian Pang, Hongwei Guan, Hong Shi. Mirk/Dyrk1B modulates the development of chemoresistance in human ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3376. doi:10.1158/1538-7445.AM2013-3376 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.