Abstract 1937: Nemo-like kinase expression is altered during prostate cancer progression

Abstract

Abstract MAPKs have been implicated in cancer progression. We have previously shown that Nemo-like kinase (NLK) inhibits androgen receptor signaling and induces apoptosis in prostate cancer cell in vitro. The objective of this study was to investigate NLK expression in clinical samples of primary prostate cancer and in prostate cancer xenografts using immunohistochemistry. TMAs containing primary prostate cancer samples and prostate cancer xenograft tissues were used. Our data show that NLK immunoreactivity is 0.34 higher in primary prostate cancer vs. normal prostate epithelium (p=0.01) but our analysis did not reveal any significant correlations of NLK immunoreactivity with PSA, Gleason score or recurrence of the disease. When we examined NLK immunoreactivity in prostate cancer xenografts our results show that there are signficant differences in cellular localization of NLK between xenografts that respond well to castration vs. those that do not. Xenografts that respond well to castration exhibit lower levels of NLK in nucleoplasm and higher leves of NLK in nucleoli vs. xenografts that do not respons well to castration (t=−4.211, p<.0001, and z=3.994, p<.0001 respectively). Our in vitro studies show that DHT increases localization of NLK in nucleoli of LNCaP. NLK levels in nucleoli negatively correlate with levels of nucleophosmin, a protein involved in regulation of proliferation, in the xenografts and in LNCaP cells in vitro. Interestingly we have also shown that in vitro NLK stimulates wnt signaling in LNCaP cells and this effecst in dependent on expresison of androgen receptor. In summary our data show that NLK expression is altered during prostate cancer progression and that NLK alters androgen receptor and wnt signaling pathways. Further studies to investigate mechanisms of NLK effects and NLK involvement in response to androgen ablation in prostate cancer are ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1937. doi:10.1158/1538-7445.AM2011-1937