Elevated levels of the cell cycle regulator cyclin D1b may be a novel biomarker of lethal metastatic disease in men with prostate cancer, a new study indicates.
As a highly oncogenic variant of the cell cycle regulator cyclin D1 (cyclin D1a), cyclin D1b is known to harbor divergent and highly oncogenic functions in cancer. Although this protein is induced during disease progression in many types of cancer, the mechanisms underlying its function remain poorly understood, explained Karen E. Knudsen, PhD, and colleagues in The Journal of Clinical Investigation (2013;123:493–508). Knudsen is the Hilary Koprowski Chair of the Departments of Cancer Biology, Urology, and Radiation Oncology at Thomas Jefferson University in Philadelphia, Pennsylvania, and Deputy Director for Basic Science at Jefferson’s Kimmel Cancer Center.
Knudsen’s investigative team found that cyclin D1b, but not cyclin D1a, regulates a large gene network. The network was shown to cooperate with androgen receptor (AR) signaling to drive metastatic progression in multiple models of prostate cancer.
The researchers also discovered that cyclin D1b expression can directly promote AR-dependent expression of the pro-metastatic gene SNA12 (Slug). This action dramatically increased metastatic events to soft tissues in animal models, affirmed Knudsen in a statement issued by Thomas Jefferson University.
“Our data describe how cross-talk between the cell cycle and AR can rewire the AR signaling axis to enhance the expression of genes [that] elicit metastasis in both early and castration-resistant prostate cancer models,” noted Knudsen in the statement. “Identification of AR-driven pathways [that] mediate metastatic progression represents a significant leap forward in our attempts to effectively manage prostate cancer progression.”