Abstract
Abstract The transcription factor NANOG is critical for the maintenance of embryonic stem cell properties including self-renewal and pluripotency. NANOG performs these functions by regulating the expression of genes required for the preservation of the stem cell phenotype. Introduction of NANOG and other embryonic stem cell genes has successfully established disease-specific induced pluripotent stem cells in several types of human cancers. Although the expression of NANOG has been documented in cancer cells, the function of NANOG in cancer has not been extensively investigated. We hypothesized that NANOG plays a role in prostate cancer cell biology based on our observation of NANOG protein expression in prostate cancer cell lines. To test this hypothesis, we transduced the PC3 prostate cancer cell line with a lentivirus capable of directing the expression of NANOG. A stable cell line containing the NANOG expression cassette was established by selection with puromycin, and expression of NANOG protein was verified by Western blot analysis. Analysis of stem cell surface markers by flow cytometry in the PC3-NANOG cells and PC3 cells transduced with empty virus revealed an increase in the percentage of CD24 positive cells in the PC3-NANOG sample as compared with the control. In addition, the density of CD24 per cell appeared to increase. This increase in CD24 expression was confirmed by Western blot analysis. In multiple cancers expression of CD24, a mucin-like adhesion protein, correlates with invasion and metastatic potential. Therefore, we conducted an invasion assay to assess the ability of PC3-NANOG cells to invade through a matrix assaying invasion by migration of cells from one chamber of a bicameral chamber through a porous membrane. The results showed that PC3-NANOG cells exhibited a 30-40% increase in invasion as compared to the control cells. (p<0.001). These results suggest that expression of NANOG in a prostate cancer cell line contributes to increased invasive capacity, possibly through enhanced expression of CD24. Therefore, NANOG could be a potential mediator of prostate cancer cell invasion and maneuvers to decrease NANOG expression could be a new therapeutic target for treatment of prostate cancer. 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 4225.
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