Role of ei24/PIG8, A Putative Pro-Apoptotic Tumor Suppressor, in Breast Cancer Development and Resistance to Drug Therapy

摘要

EI24/PIG8 is regulated by p53 in response to genotoxic damage and was shown to be genetically inactivated in aggressive breast cancers with frequent loss-of-heterozygosity. In addition, it was shown that ectopic expression of EI24/P108 resulted in apoptosis, whereas suppression of E124/PIO8 expression resulted in increased survival after treatment with an apoptotic retinoid. We hypothesizid that genetic inactivation of EI24/PIO8 is a major contributing factor to breast cancer development and resistance to chemotherapeutic agents such as etoposide. We recently found evidence that EI24/PIO8 directly binds with Bcl-2 in the endoplasmatic reticulum (ER), and likely initiates apoptosis at this organelle by altering the activity of ER- resident Bcl-2 (purpose of Objectives 1 and 2). Our studies also showed that EI24/PIG8 likely serves to suppress tumor spreading, rather than formation of the primary tumor. Thus, the EI24/PI08 status of breast cancers may serve as a potential novel prognostic indicator in this disease.