Free radicals may increase androgen receptor function

[purecontrol]

1: Clin Cancer Res. 2008 Oct 1;14(19):6073-80.
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Effects of manganese superoxide dismutase silencing on androgen receptor function and gene regulation: implications for castration-resistant prostate cancer.

Sharifi N, Hurt EM, Thomas SB, Farrar WL.

Authors' Affiliations: Cancer Stem Cell Section, Laboratory of Cancer Prevention, National Cancer Institute at Frederick, Center for Cancer Research, National Cancer Institute.

PURPOSE: Advanced prostate cancer is first treated with androgen deprivation therapy. However, tumors become resistant to and grow despite castrate levels of testosterone. Growth and proliferation of CRPC is mediated by gain-of-function changes in the AR and AR reactivation. Expression of manganese superoxide dismutase (SOD2), which regulates cellular ROS, is markedly down-regulated in CRPC when compared with hormone-responsive tumors. EXPERIMENTAL DESIGN: Here, we knocked down SOD2 expression in AR-expressing LNCaP prostate cancer cells and determined gene expression changes, transcription factor binding, and AR transcription activity in SOD2 knockdown cells. RESULTS: SOD2 knockdown results in an increase in ROS. Gene expression changes induced by SOD2 knockdown results in the up-regulation of genes that are also androgen responsive and 46% of genes up-regulated 2-fold by the androgen ligand R1881 are also up-regulated to the same extent with SOD2 knockdown. The induction of many of these genes with SOD2 knockdown, such as VEGFA and FKBP5, is reversible with the antioxidant N-acetylcysteine, suggesting that this mechanism is directly linked to ROS. Furthermore, an array for transcription factor DNA-binding activity shows that SOD2 knockdown induces DNA binding by several transcription factors, including AR. SOD2 knockdown-induced AR activation was confirmed by electrophoretic mobility shift assay and luciferase activity, and both were readily reversible with N-acetylcysteine. CONCLUSIONS: These findings show that down-regulation of SOD2 induces AR activity in a ROS-dependent manner, and suggest that there may be a role for antioxidant therapy in CRPC.

PMID: 18829485

There you have it, yet another reason why AOs are so important.

 

[elguapo]

I am sick and tired of the word "may". "This or that MAY have this or that effect." F*ck may!!! Get us some gd proof or shut the hell up! Not 60 or 70 or 97 percent of the time, but 100% of the fing time!

Mankind sucks! We are stupid stupid stupid!!! We are slipping into debt here in the US, we know the system is broken, and yet we don't fix it.... we are going nowhere fast!

 

[Petchsky]

Sounds like your having a real bad day elguapo, stay away from the newspapers, the word MAY, appears all the f*****g time.

 

[Bryan]

Scientists are naturally cautious, and have an aversion to making dogmatic statements about anything; hence, their frequent use of the word "may".

Case in point: the original poster "purecontrol" would also be well-advised to use caution when making wild claims about his estrogen/male pattern baldness theory!