Accession Number : AD1050562


Title :   Study the Origin and Mechanisms of Castration Resistance Characterized by Outgrowth of Prostate Cancer Cells with Low/Negative Androgen Receptor


Descriptive Note : Technical Report,15 Sep 2015,14 Sep 2017


Corporate Author : Sloan Kettering Institute for Cancer Research New York United States


Personal Author(s) : Lee, Eugine


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1050562.pdf


Report Date : 01 Dec 2017


Pagination or Media Count : 26


Abstract : While the association of androgen receptor (AR) amplification with poor clinical outcome is well known in prostate cancer, the impact of AR signaling level to treatment response has not been studied. Our data suggests that in primary prostate cancer where there are rare events of AR amplification, the level of AR activity might be able to distinguish aggressive disease. When we isolated cells with low and high AR activities, the tumors derived from cells with high AR activity acquired resistance to enzalutamide faster, implying the clinical implication of varying AR activities. We also identified three AR regulated genes,GREB1, KLF8 and GHRHR, upregulated in cells with high AR activity and promoted AR transcriptional output in a feed back mechanism. Given the known function of GREB1 as an ER cofactor, we selected GREB1 for further study and found thatGREB1 amplifies AR transcriptional activity and potentially promote enzalutamide resistance. Further understanding of the molecular function of GREB1 will provide novel insights into the development of effective therapeutic approaches to treat enzalutamide resistant prostate cancer.


Descriptors :   prostate cancer , androgens , genes , transcription (genetics) , drug resistance , gene expression , neoplasms , inhibitors


Subject Categories : Medicine and Medical Research
      Genetic Engineering and Molecular Biology
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE