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JunD mediates androgen-induced oxidative stress in androgen dependent LNCaP human prostate cancer cells.

Authors :
Mehraein-Ghomi F
Lee E
Church DR
Thompson TA
Basu HS
Wilding G
Source :
The Prostate [Prostate] 2008 Jun 15; Vol. 68 (9), pp. 924-34.
Publication Year :
2008

Abstract

Background: Numerous and compelling evidence shows that high level of reactive oxygen species (ROS) plays a key role in prostate cancer occurrence, recurrence and progression. The molecular mechanism of ROS overproduction in the prostate gland, however, remains mostly unknown. Unique AP-1 transcription factor JunD has been shown to inhibit cell proliferation, promote differentiation and mediate stress responses in a variety of eukaryotic cells. We previously reported that androgen-androgen receptor induced ROS production in androgen-dependent LNCaP human prostate cancer cells is associated with increased JunD level/AP-1 transcriptional activity.<br />Methods: LNCaP cells constitutively overexpressing a functionally inactive form of JunD (JunDDeltaTA) or stably transfected with JunD siRNA (siJunD) to suppress JunD protein expression were established. Overexpression of JunD in LNCaP cells using transient transfection method was applied to assess the induction of ROS production in LNCaP cells. DCF assay was used to measure the ROS concentrations in the transfected as well as non-transfected control cells. RT-PCR and Western blot analyses were used to confirm silencing or overexpression of JunD in the transfected cells.<br />Results: In the absence of androgen, LNCaP cells transiently transfected with a JunD overexpressing vector have relatively enhanced cellular ROS levels as compared to LNCaP cells transfected with a vector control. LNCaP cells that fail to express functional JunD (JunDDeltaTA or siJunD) do not exhibit any increase in ROS production in response to androgen.<br />Conclusion: Based on these data, we conclude that JunD is an essential mediator of the androgen-induced increase in ROS levels in LNCaP cells.

Details

Language :
English
ISSN :
0270-4137
Volume :
68
Issue :
9
Database :
MEDLINE
Journal :
The Prostate
Publication Type :
Academic Journal
Accession number :
18386285
Full Text :
https://doi.org/10.1002/pros.20737