Role of Oncogene/Tumor Suppressor Interaction with the Centrosome Protein Pericentrin in Prostate Tumorigenesis

摘要

Prostate carcinoma is the most common form of cancer in American men. The etiology of prostate cancer is currently unknown. It is known that during progression from low to high-grade carcinoma, the spectrum of cytologic, biological, and genetic features changes. We believe that these changes may be a result of defects in the centrosome, an essential organelle that organizes spindle poles during mitosis and has important roles in cell proliferation, cell polarity, and genetic stability. We have shown that centrosomes are defective in prostate carcinoma and pre-invasive lesions. We also showed that the essential centrosomal protein pericentrin is elevated in both pre-invasive prostate lesions and invasive prostate tumors, induces cancer like lesions when overexpressed and binds AKT, PKA and PKC. In this proposal we will follow up on these observations by: examining pericentrin's oncogenic potential after disrupting its interactions with the kinases AKT, PKA and PKC and determine whether other oncogenes or tumor suppressors act synergistically or antagonistically with pericentrin in prostate cancer.