Abstract
Abstract
Introduction: Inhibitor of DNA binding 4 (ID4), a bHLH protein and a transcriptional regulator, is a tumor suppressor gene in prostate cancer. ID4 is expressed in prostate cancer cells (LNCaP), which are androgen sensitive, but epigenetically silenced in a more aggressive DU145 cells. The epigenetic silencing of ID4 is associated with increasing tumor grade and castration resistant prostate cancer (CRPC). ID4 regulates the expression of some other genes such as SAT1, which is a rate limiting enzyme found in the X chromosome involved in the catabolic pathway of polyamine metabolism by catalyzing the N(1)-acetylation of spermidine and spermine. Recently, SAT1 was also shown to mediate histone H3 acetylation suggesting its role in regulating gene expression. Next generation sequencing (NGS) data showed a significant low expression of SAT1 when ID4 is up regulated and vise-versa, which led to a hypothesis that ID4 might regulate the expression of SAT1 gene in prostate cancer cells.
Experimental procedures: The NGS (exon sequencing) was performed on prostate cancer cells either over-expressing ID4 (DU145(+)ID4) or cells in which ID4 was genetically silenced (LNCaP(-)ID4). Moreover, immunohistochemistry (IHC) analysis was performed on mice prostates tissues (WT and ID4-/- mice) and DU145(+)ID4 tumor xenografts tissues to analyze SAT1 protein expression in the presence and the absence of ID4.
Results: The NGS and IHC data analysis suggested that Spermidine/spermine N(1)-acetyltransferase (SAT1) is up-regulated in cells lacking ID4 such as (LNCaP(-)ID4) but down-regulated in cells which express ID4 (DU145(+)ID4). These results prompted us to investigate the effect of silencing SAT1 on ID4 expression and on cancer phenotype.
Conclusion: The expression of ID4 gene in prostate cancer cell lines LNCaP, and DU145(+)ID4 cells showed low expression of SAT1 gene compared with cells lacking ID4 gene as in LNCaP(-)ID4 and DU145 cells.
Acknowledgment: These studies were supported by the NIH/NIMHD/P20 Grant
#P20MD002285.
Citation Format: Majid Al-Zahrani. The role of ID4 in regulating SAT1 gene expression in prostate cancer phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5301.