关键词：脱氧核糖核的酸;基因;前列腺癌;细胞(生物学);临床医学
摘 要：The research goals of this grant proposal are to: (1) investigate the effect of ETS gene fusions on radiation phenotype in pre-clinical models of prostate cancer, (2) to explore the mechanism of interaction between ERG (the predominant ETS gene fusion product) and the DNA repair protein DNA-PK, and (3) to determine if ETS gene fusion status is a clinical biomarker of radioresistance for prostate cancer. The training goals of this grant proposal included a series of regular meetings with mentors, research seminars, journal clubs, and workshops, all of which are intended to help Dr. Feng develop as a translational scientist. This grant proposal was approved as a five-year award; the current annual report summarizes accomplishments over the second year of the grant, from July 15, 2011 to July 15, 2012. Overall, the first two years of this grant have been very successful. The work accomplished as a result of this grant resulted in two publications in very high impact journals, four national presentations, and three grants (two from the Prostate Cancer Foundation and one from Celgene). Additionally, Dr. Feng has met the training achievements specified in his original grant. The research proposed in this training grant represents an important area within the field of prostate cancer research. Because ETS gene fusions are thought to be driver alterations in over half of all prostate cancers, understanding the mecha-nistic and potential clinical implications of these gene fusions has significant ramifications, particularly in the context of radiation therapy, which represents a primary treatment modality for localized prostate cancer. In the second year of this grant period, we have generated bioluminescent ETS+ and ETS- cells in three different prostate cancer cell lines, and we havereceived institutional approval to proceed with the proposed animal studies and human biomarker tissue studies.