Basic Research - Cancer(구연) (E-014)

신장암에서 안드로겐 수용체 활성도 조절을 통한 히스톤 디메틸라제 LSD1의 질병진행 억제역할 규명 연구
1. 서울대학교병원 비뇨의학과
2. 카이스트 의생명공학과
서준교1, 이경화1, 김병창1, 정승환2, 정창욱1, 구자현1, 김현회1, 곽철1
Kidney cancer is one of most difficult cancers to treat by targeted and radiation therapy. Therefore, identifying key regulators in this cancer is especially important for finding new drugs. We focused on androgen receptor (AR) regulation by its epigenetic co-regulator histone demethylase LSD1 in kidney cancer development. LSD1 knock-down in kidney cancer cells decreased expression of AR target genes. Moreover, binding of AR on target gene promoters was reduced and histone methylation status was changed in LSD1 knock-down kidney cancer cells. LSD1 knock-down also slowed growth and decreased migration ability of kidney cancer cells. We found that pargyline, known as LSD1 inhibitor, can reduce AR activity in kidney cancer cells. Treatment of kidney cancer cells with pargyline delayed growth and repressed EMT markers. These effects were synergistically enhanced by co-treatment with AR inhibitor enzalutamide. Down-regulation of LSD1 in renal cancer cells (RCC) attenuated in vivo tumour growth in a xenograft mouse model. These results provide the evidences that LSD1 can regulates kidney cancer cell growth via epigenetic control of AR transcription factor and that LSD1 inhibitors may be good candidate drugs for treating kidney cancer.
keywords : Androgen Receptor, Histone methylation, LSD1, Kidney cancer, Enzalutamide