Open AccessHypoxia upregulates Hsp90α expression via STAT5b in cancer cells
Author(s) -
Se Hyung Pak,
Youn Hee Joung,
Jin Hee Park,
Eun Joung Lim,
Pramod Darvin,
Yoon Mi Na,
Dae Young Hong,
Boram Lee,
Tae Sook Hwang,
Taegyu Park,
Sang Kyu Ye,
Eon Soo Moon,
Byung Wook Cho,
Kyung Do Park,
Hak Kyo Lee,
Ill Min Chung,
Young Mok Yang
Publication year - 2012
Publication title -
international journal of oncology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2012.1450
Subject(s) - hsp90 , biology , oncogene , cancer research , rna interference , signal transduction , transcription factor , hsp90 inhibitor , hypoxia (environmental) , microbiology and biotechnology , cancer , cell cycle , gene , heat shock protein , rna , genetics , chemistry , organic chemistry , oxygen
Hsp90α is a molecular chaperone protein involved in the structural maturation of oncogenic signaling proteins. Hsp90 was recently identified as an anticancer target; various studies are ongoing to find ways for managing cancer through Hsp90α. However, this approach is limited by reported side-effects. Hypoxia is a hallmark of solid tumors, including those of breast cancer and the extent of tumor hypoxia is associated with resistance to treatment and poor prognosis. One of the major signaling pathways in cancer cells, the Jak2/STAT5b pathway, has been found to be closely correlated with hypoxia. The objective of this study was to investigate the role of Jak2/STAT5b in the regulation of Hsp90α expression so that Hsp90α targeting can be achieved indirectly by modulating the Jak2/STAT5b pathway. We examined the role of the Jak2/STAT5b pathway in the expression of Hsp90α under hypoxic conditions by immunoblotting, reporter gene assays, EMSA and RNA interference analysis. With the help of in vivo models, we also analyzed the expression of Hsp90α in different parts of solid tumor tissues. We found a close association between hypoxic stress and Hsp90α expression. We also determined that STAT5b regulates the expression of Hsp90α during hypoxic stimulation. Under hypoxic conditions the expression of Hsp90α and STAT5b were proportional. siRNA analysis and nucleotide analysis showed that the promoter of Hsp90α has a STAT5b binding domain. Our work confirmed that STAT5b is one of the transcription factors that regulate Hsp90α. We, therefore, concluded that under hypoxic conditions, the Jak2/STAT5b pathway regulates Hsp90α expression and it could serve as a promising target for the treatment of solid tumors.