The Role of GGAP2 in Prostate Cancer
Abstract
The major goal of this study is to characterize the functions and expression profile of GGAP2 in human PC (HPC). Our data show that GGAP2 protein expression is increased in HPC in both HPC cell lines and clinical patient samples. Biochemical studies indicate that GGAP2 activate both AKT and NF-kB pathways and can promote HPC growth at cellular level and in mouse model. Using PCR with > 100 clinical HPC tissue samples, cloning and direct sequencing, we found that multiple low-frequency mutations may exist in PC. Our data showed some of these mutations activate the GTPase domain of GGAP2 and enhance its effects on cancer growth. PC3 cells stably expressing wild-type GGAP2 form larger volume tumors in nude mice model when compared to control, while knockdown of GGAP2 or overexpressing the dominant negative form GGAP2 S629A dramatically inhibit tumor growth. These findings indicate that GGAP2 may function as an important modulator in HPC which can regulate both AKT and NF-kB pathways. This assists us to understand better the mechanism of HPC development. Detection methods and novel therapeutic tools targeting GGAP2 specifically may be successful in reducing HPC incidence and slow down cancer development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2009
- Accession Number
- ADA502642
Entities
People
- Michael M. Ittmann
- Yi Cai
Organizations
- Baylor College of Medicine