BSCRC Director Owen Witte and colleagues discover key mechanism that regulates prostate stem cell self-renewal

A protein that is crucial for regulating the self-renewal of normal prostate stem cells, needed to repair injured cells or restore normal cells killed by hormone withdrawal therapy for cancer, also aids the transformation of healthy cells into prostate cancer cells, researchers at UCLA have found.

The findings, by researchers with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, may have important implications for controlling cancer growth and progression.

Done in primary cells and in animal models, the findings from the three-year study appear Dec. 2, 2010 in the early online edition of the peer-reviewed journal Cell Stem Cell.

The protein, called Bmi-1, is often up-regulated in prostate cancer, has been associated with higher grade cancers and is predictive of poor prognosis, according to previous studies. However, its functional roles in prostate stem cell maintenance and prostate cancer have been unclear, said Dr. Owen Witte, who is director of the Broad Stem Cell Research Center, a Howard Hughes Medical Institute investigator and senior author of the study.

A study of loss and gain of function in prostate stem cells indicated that Bmi-1 expression was required for self-renewal activity and maintenance of prostate stem cells with highly proliferative abilities. Loss of Bmi-1 expression blocks the self-renewal activity, protecting prostate cells from developing abnormal growth changes which can lead to cancer.

More importantly, Bmi-1 inhibition slowed the growth of an aggressive form of prostate cancer in animal models, in which the PTEN tumor suppressor gene was removed allowing the cancer to run wild, Witte said.

“We conclude by these results that Bmi-1 is a crucial regulator of self-renewal in adult prostate cells and plays important roles in prostate cancer initiation and progression,” Witte said. “It was encouraging to see that inhibiting this protein slows the growth of even a very aggressive prostate cancer, because that could give us new ways to attack this disease.”