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ELL is an HIF‐1α partner that regulates and responds to hypoxia response in PC3 cells
Author(s) -
Liu Lingqi,
Ai Junkui,
Xiao Wuhan,
Liu June,
Wang Yujuan,
Xin Dianqi,
He Zhisong,
Guo Yinglu,
Wang Zhou
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21113
Subject(s) - gene knockdown , hypoxia (environmental) , transfection , biology , transcription factor , western blot , microbiology and biotechnology , carcinogenesis , cell growth , hypoxia inducible factors , immunoprecipitation , gene , chemistry , biochemistry , oxygen , organic chemistry
BACKGROUND Eleven–nineteen lysine‐rich leukemia (ELL) plays an important role in tumorigenesis and animal development. HIF‐1 is a transcriptional factor that functions as a master regulator of O 2 homeostasis. Our previous studies showed that a binding partner of ELL, U19/Eaf2, can modulate HIF‐1α activity and hypoxia response, suggesting that ELL may also influence HIF‐1α pathway and hypoxia response. METHODS Co‐localization and co‐immunoprecipitation were performed to test the interaction between ELL and HIF‐1α. PC3 cells with stable ELL knockdown and PC3 cells with stable ELL overexpression, along with their controls, were established using lentiviral expression system. Western blot and real‐time PCR were performed to test the effect of ELL on HIF‐1α protein and its down‐stream gene transcription. To elucidate potential effect of hypoxia on ELL, cell growth and colony formation assays were performed using PC3 subline with stable ELL overexpression. RESULTS ELL is associated with HIF‐1α in transfected cells. In PC3 prostate cancer cells, ELL inhibited HIF‐1α protein level and down‐stream gene expression. As expected, ELL inhibited cell growth and colony formation under normoxia. Interestingly, the inhibition was alleviated under hypoxia. CONCLUSIONS Our findings suggest that ELL and HIF‐1α are binding partners and can modulate the functions of each other in hypoxia. Prostate 70: 797–805, 2010. © 2010 Wiley‐Liss, Inc.