Prostate cancer: Androgen receptor activates different genes when bound to antiandrogens

PUBLIC RELEASE 01/27: The androgen receptor in prostate cancer cells can activate different sets of genes depending on whether it binds with an androgen hormone or an antiandrogen drug, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
The study found that when androgen receptor (AR) binds with testosterone or dihydrotestosterone, the activated receptor binds, as expected, to segments of DNA called androgen response elements.
But when the receptor binds with either of two antiandrogenic drugs, bicalutamide or enzalutamide, it then binds to different DNA sequences and activates entirely different sets of genes, including cancer-promoting oncogenes.
The researchers called these newly discovered AR binding sites on DNA "antiandrogen response elements" and showed that they activate genes that might enable tumor progression during antiandrogen treatment.
The findings suggest that the treatment of prostate cancer with antiandrogenic drugs should include agents that target antiandrogen-regulated oncogenes.
"The discovery of antiandrogen response elements was completely unexpected," says principal investigator and researcher Qianben Wang, PhD, associate professor of molecular virology, immunology and medical genetics.
He noted that antiandrogen agents are known to work by competing with androgens to bind to AR, thus inhibiting androgen-induced gene expression.
"We found that antiandrogens can also trigger AR to bind to DNA sequences that are distinctly different from androgen response elements, and thus regulate genes relevant to prostate cancer development," Wang says.
Prostate cancer is the most frequently diagnosed cancer in men. An estimated 220,800 new cases are expected in the United States in 2015, along with 27,540 deaths from the disease.