커뮤니티

Global Group

Best your Partner

초청세미나

게시글 검색
종양연구소 초청세미나 (2014.11.27)
종양연구소 조회수:600
2017-05-18 15:58:06

충북대학교 종양연구소에서 다음과 같이 초청세미나를 개최하오니 많은 참여 부탁드립니다.

                                  -    다    음   -

1. 연 자  :  현 진 원 교수 (제주대학교)

2. 일 시  :  2014년 11월 27일 (목)  오후 4시

3. 연 제  :  Involvement of DNA demethylase, ten-eleven translocation, in 5-fluorouracil resistant

               colorectal cancer cells.

4. 장 소  :  종양연구소 세미나실 104호 

5. 발 표 내 용

An anticancer drug, 5-fluorouracil (5-FU) is widely used for the treatment of colorectal cancer (CRC). However, resistance to 5-FU often prevents the success of chemotherapy. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional regulator and a possible target to overcome 5-FU resistance. The present study examined epigenetic changes associated with Nrf2 induction in a human CRC cell line (SNUC5) resistant to 5-FU (SNUC5/5-FUR). The mRNA and protein expression of heme oxygenase-1 (HO-1), an Nrf2-regulated gene, were higher in SNUC5/5-FUR cells than in SNUC5 cells. Furthermore, Nrf2 expression, nuclear translocation, and binding to HO-1 promoter were higher in SNUC5/5-FUR cells than in SNUC5 cells. SNUC5/5-FUR cells produced a larger amount of reactive oxygen species (ROS) than SNUC5 cells. siRNA- or shRNA-mediated knockdown of Nrf2 or HO-1 significantly suppressed cancer cell viability and tumor growth in vitro and in vivo, resulting in enhanced 5-FU sensitivity. Methylation-specific or quantitative PCR showed hypomethylation of the Nrf2 promoter CpG islands in SNUC5/5-FUR cells compared to SNUC5 cells. Expression of the DNA demethylase ten-eleven translocation 1 (TET1) was upregulated in SNUC5/5-FUR cells. The enhanced interaction between TET1 and O-GlcNAc transferase, a regulator of TET1, increased the affinity of TET1 for the Nrf2 promoter and promoted TET1 function in SNUC5/5-FUR cells. ROS generated by 5-FU upregulated TET1 expression and function in SNUC5 cells, whereas antioxidant had the opposite effect. These results suggested that the mechanism underlying the acquisition of 5-FU resistance in CRC involves the upregulation of Nrf2 and HO-1 expression via epigenetic modifications including DNA demethylation.

SNS 공유