Introduction/Background Endometrial cancer (EC) is the fourth most common cancer in women in the UK. The role of androgen in EC has not been as heavily studied as the integral roles of oestrogen and progesterone. While in vivo studies successfully targeted androgen receptor (AR) as a therapeutic target, the exact way the AR enacts its effects on a cellular level remains poorly understood. We aim to explore the transcriptional changes in response to AR activation in EC cell lines as well as investigate the AR primary target binding sites.

Methodology Ishikawa EC cell line was transduced with AR and treated with 1nM of synthetic androgen (R1881). RNA was extracted and Next Generation Sequencing (RNA-seq) was performed. Results were analysed in conjunction with RNA-seq of AR-dependant prostate cancer LNCaP cell line +/- R1881 exposure. Integrative analysis was undertaken with publicly available LNCaP chromatin immunoprecipitation (ChIP) sequencing.

Results Approximately 2617 genes showed statistically significant differential expression in response to R1881 exposure in the AR-transduced Ishikawa EC cell line, with 1400 differentially expressed genes (DEGs) in common with LNCaP cell line +/- R1881. Out of all differential binding sites in the LNCaP ChIP-seq in response to R1881 exposure, 334 peaks, corresponding to 230 DEGs in the transcriptomic analysis of both Ishikawa and LNCaP cell line, were observed. These genes included PPFIBP2, SEMA6A, STXBP6, and KLHL13 and potentially represent a subset of AR-specific DNA bindings sites common between endometrial and prostate cancer cell lines.

Conclusion We successfully established and validated an AR-overexpressing EC cell line. The transcriptional profile changes in response to R1881 stimulation are typical of AR-mediated effects. Integrative analysis with ChIP-seq dataset identified a list of potential AR primary target binding sites. We aim to use these target sites to optimise ChIP technique in Ishikawa cells followed by ChIP-seq with R1881 stimulation.

Disclosures No disclosures.