First Steps

Prostate Progress
(continued)

But only for a while. With deadly cunning, prostate cancer cells eventually adapt to an androgen-depleted environment. They become androgen independent — able to grow without testosterone. When this happens, few treatment options remain.

Ralph deVere White, director of the UC Davis Cancer Center, is a leading investigator into androgen independence. “If we could prevent it from happening,” he said, “it would have a dramatic impact on treatment and outcomes for prostate cancer.”

Enter p53. P53 is a protein that is supposed to prevent normal cells from proliferating out of control. When p53 fails to work, cancer results.

DeVere White’s laboratory was the first to show that two out of every three men with androgen-independent prostate cancer have p53 mutations. While many in the field wrote this off as mere coincidence, deVere White believed otherwise.

“It made no sense to me,” he said. “Why would you presume p53 mutations are just along for the ride? It’s been our belief that at least in some cases, those mutations are allowing prostate cancer cells to live without androgen.”

To test the theory, deVere White and Shi experimented with a well-known androgen-dependent prostate cancer cell line. They added a p53 mutation known as R273H to the cell line, then waited to see what happened. What they found confirmed their hypothesis. The line of cells, once dependent on androgen, now grew in an androgen-free laboratory dish. The cells also grew when injected beneath the skin of female mice, which, by virtue of their gender, lack male hormones.

“To our knowledge, this is one of the first proofs that a p53 mutation in prostate cancer cells confers androgen-independent growth,” deVere White said.