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Identification of the KAI1 metastasis suppressor gene as a hypoxia target gene

Cited 7 time in Web of Science Cited 11 time in Scopus
Authors
Kim, Bogyou; Boo, Kyungjin; Lee, Jason S.; Kim, Keun Il; Cho, Hyun-Jai; Kim, Hyo-Soo; Baek, Sung Hee; Park, Young-Bae; Kim, Woo Ho
Issue Date
2010-02-26
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS; Vol.393 1; 179-184
Keywords
CancerMetastasisTranscriptionHypoxiaSuppressor
Abstract
KAI1 is a metastasis suppressor gene known to inhibit cancer metastasis without affecting primary tumorigenicity. Although KAI1 expression has been reported to undergo transcriptional regulation, how its expression is up- or down-regulated by specific upstream signaling pathways has not been studied in detail. In this study, we characterized the regulatory elements within the 500 bp upstream region of mouse KAI1 gene and identified a functional hypoxia-response element (HRE) within the promoter region. Hypoxia-dependent induction of KAI1 was directly mediated by hypoxia-inducible factor (HIF)-1 alpha binding on the promoter, which subsequently caused increased recruitment of RNA polymerase II for transcriptional activation. The failure of HIF-1 alpha recruitment to the KAI1 promoter was observed in Hif-1 alpha knockout mouse embryonic fibroblasts. Furthermore, KAI1 protein synthesis was markedly increased in ischemic tissues, suggesting that KAI1 is a hypoxia target gene in vivo. (C) 2010 Elsevier Inc. All rights reserved.
ISSN
0006-291X
Language
English
URI
http://hdl.handle.net/10371/76687
DOI
https://doi.org/10.1016/j.bbrc.2010.01.118
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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