새로운 혈관신생인자인 이슐린-유사 성장인자 II (IGF-II)의 전사조절에 관한 연구
Regulation of Transcriptional Activity of Insulin-like Growth Factor II (IGF-II)
배명호, 송현석, 배수경, 이석기, 이세원, 김철우, 김규원,
소속 상세정보
배명호 ( Bae Myung-Ho )
부산대학교 분자생물학과
송현석 ( Song Hyun-Seok )
부산대학교 분자생물학과
배수경 ( Bae Soo-Kyung )
부산대학교 분자생물학과
이석기 ( Lee Seok-Ki )
서울대학교 약학대학
이세원 ( Lee Sae-Won )
서울대학교 약학대학
김철우 ( Kim Chul-Woo )
서울대학교 의과대학 병리학교실
김규원 ( Kim Kyu-Won )
서울대학교 약학대학
KMID : 0603520020070010027
Abstract
It has been known that IGF-II is required for normal pre-natal growth of the liver in rodents and humans and has an angiogenic effect in experimental animals. The human IGF-II gene is a complex transcription unit containing four different promoters, leading to the formation of multiple IGF-II mRNA. The four promoters can be activated in a development-dependent and tissue-dependent manner. The human IGF-II promoter P3 is used in many fetal tissues and is highly active in several tumors, suggesting autocrine effects of IGF-II in tumor progression. In this study, we confirmed increased transcriptional activity of IGF-II P3 promoter under hypoxia. In addition, we showed that MAPK pathway is not involved in activation mechanism of IGF-II P3 promoter by using MAPK nhibitors and JNK dominant negative mutants. Moreover, we investigated the effect of hypoxia on the transcriptional activity of Egr-l, possible transcription factor regu1ating IGF-II. These results may examine the molecular signaling mechanism of carcinogenesis and metastasis in hepatocellular carcinoma and can apply to the development of cancer diagnosis and therapy.
키워드
Insulin like Growth Factor-I;; Mitogen activated protein kinase;Transcriptional activity; Hypoxia
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