|[교육과학기술부·한국연구재단 지정 한림대학교 생명공학연구소]
◎ 제5차 생명공학연구소 정기세미나 개최 ◎
Id-1 is a crucial player in mammary gland development and carcinogenesis
Inhibitor of differentiation-1 (Id-1) has been accepted as a putative oncogene to promote oncogenic processes through inactivation of tumor suppressors and activation of growth promoting pathways. Recently, we have reported the crucial roles of Id-1 in mammary development and carcinogenesis.
Firstly, we have found that Id-1 is involved in tumor angiogenesis. Id-1 induced vascular endothelial growth factor (VEGF) by enhancing the stability and activity of HIF-1alpha in human endothelial and breast cancer cells. This led to transcriptional activation of HIF-1-dependent promoters and induction of tube formation in human umbilical endothelial cells (HUVEC). Furthermore, Id-1 overexpression is significantly associated with tumor angiogenesis in ER-negative/node-positive breast cancer.
Secondly, we demonstrated that Id-1 played a protective role against anti-cancer drug-induced apoptosis. Id-1 regulated Bcl-2 and Bax expression through p53 and NF-kappaB pathways in MCF-7 breast cancer cells. This provided a survival advantage under exogenous stress such as serum-free or taxol treatment.
Thirdly, our results disclose Id-1 as a novel inhibitor of PTEN that could activate the Akt pathway. Id-1 negatively regulated PTEN transcription through downregulation of p53, a transactivator of PTEN. Reduced PTEN expression led to activation of the Akt and its downstream effectors, the Wnt/TCF pathway and p27Kip1 phosphorylation.
Fourthly, we have recently investigated the possibility that Id-1 might be an epigenetic and cancer stem cell regulator through regulation of polycomb group (PcG) proteins. Id-1 was able to regulate expression of Mel-18 and Bmi-1, which belong to polycomb repressive complex 1 (PRC1). Particularly, Id-1 enhanced c-Myc-mediated transcription of Bmi-1, a crucial stem cell marker.
aFinally, we have found the critical role of Id-1 in mammary gland development using MMTV-Id-1 transgenic mice. Accelerated ductal extension, excessive side-branching and precocious lobuloalveolar development were shown in virgin MMTV-Id-1 transgenic mice. Moreover, Id-1 increased alveolar growth and secretory differentiation during pregnancy and delayed apoptosis during involution. Furthermore, increased tumor incidence rates were seen in MMTV-Id-1 mice. Conclusively, our data suggest that Id-1 plays an important role in breast carcinogenesis and mammary gland development through regulation of many biological processes such as cell growth, survival, and tumor angiogenesis and could provide Id-1 as a possible therapeutic anti-tumor target molecule in breast cancer.
아래의 연사분을 초청하여 제 5차 정기세미나를 개최하오니 많은 참석 부탁드리겠습니다.
- 다 음-
▶ 일 시 : 2010. 6. 8(화) 오후 5시
▶ 장 소 : 산학협력단 세미나실(12102호실)
▶ 연 자 : 공구 교수(한양대학교)
▶ 주 최 : 생명공학연구소
▶ 연사 학력 및 경력
1982 서라벌 고등학교 졸업
1988 한양대학교 의학학사
2000 한양대학교 의학박사