ELL is an HIF-1alpha partner that regulates and responds to hypoxia response in PC3 cells.
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-1alpha activity and hypoxia response, suggesting that ELL may also influence HIF-1alpha pathway and hypoxia response.


METHODS
Co-localization and co-immunoprecipitation were performed to test the interaction between ELL and HIF-1alpha. 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-1alpha 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-1alpha in transfected cells. In PC3 prostate cancer cells, ELL inhibited HIF-1alpha 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-1alpha are binding partners and can modulate the functions of each other in hypoxia.
Liu
Lingqi
L
Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing, China.
Ai
Junkui
J
Xiao
Wuhan
W
Liu
June
J
Wang
Yujuan
Y
Xin
Dianqi
D
He
Zhisong
Z
Guo
Yinglu
Y
Wang
Zhou
Z
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D008297:Male; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
C090862:ELL protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D035602:Transcriptional Elongation Factors