The results of recent research projects give new insight into the development of androgen independence by prostate cancer cells, according to a presentation at the Annual Meeting of the American Urological Association.

Nearly 190,000 American men develop prostate cancer every year, and a substantial proportion requires androgen suppression therapy. However, the therapy eventually fails as cancer cells develop androgen independence.

"If we could prevent androgen independence from happening, it would have a dramatic impact on treatment and outcomes for prostate cancer," said Dr. Ralph deVere White, chair of urology at the university where the research was conducted.

Two of the studies reported new information about the role of the p53 gene in androgen independence. Mutations in p53 are seen in roughly two thirds of prostate cancers that have developed androgen independence. In one of the studies, deVere White and his colleagues demonstrated that 4 particular p53 mutations -- G245S, R248W, R273C, and R273H -- facilitate androgen-independent growth of human prostate cells.

The researchers were able to grow the 4 mutant cell lines in androgen-free conditions both in cell culture and in female mice. In addition, they successfully used siRNA technology to target an siRNA molecule to the R273H mutation and suppress its activity, a finding that suggests siRNA technology may have therapeutic value in the treatment of hormone-independent prostate cancer.

In a second study, Dr. Clifford G. Tepper and his colleagues used microarray technology to hunt for specific genes that contribute to androgen independence. They reported that overexpression of a particular gene, Id-1, is a feature of androgen-independent tumors that have p53 mutations. In order to identify the Id-1 gene, researchers profiled more than 12,000 genes in cells with a p53 mutation. The Id-1 gene was shown to produce a protein that suppresses cell aging and promotes tumor aggressiveness.

The authors hope that further research will lead to interventions that can block development of androgen independence or reverse (at least in part) the effect of the genetic changes that underlie hormone-independent growth.