Abstract 5330: Androgen independent promotion of prostate cancer cell invasion by HOXB13-mediated zinc regulation

Abstract

Abstract A healthy prostate maintains the high level of zinc while intracellular zinc is diminished during prostate cancer (PCa) developments. However, down-regulation of intracellular zinc in PCa are not fully understood, particularly in development of hormone refractory PCa (HRPC). Our previous studies showed that HOXB13 was overexpressed in HRPC. In our attempt to profile androgen-independent HOXB13 target genes in LNCaP PCa cells by DNA microarray, most strikingly regulated gene was ZnTs, a group of zinc output transporters. HOXB13 drove PCa cells to decrease intracellular zinc concentration. In the absence of androgen, HOXB13 dramatically promoted NF-κB-mediated signaling by reduction of inhibitor of NF-κB alpha (IκBα) and correspondingly stimulated nuclear translocation of RelA/p65. HOXB13-mediated NF-κB activation was nearly eliminated by suppression of ZnT4. At the same time, prostate tumors strongly indicated inverse correlation of HOXB13 and IκBα expression. Correspondingly, HOXB13 stimulated an invasive property of LNCaP cells, which can be negated by suppression of ZnT4 in an androgen-free environment. Taken together, these results demonstrate that HOXB13 promoted PCa cell invasion in an androgen-deprived condition by decreasing intracellular zinc concentration to further stimulate NF-κB-mediated transactivation, indicating that HOXB13 overexpression contributes to the malignant biological behavior of HRPC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5330. doi:1538-7445.AM2012-5330