* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Sarah Justvig (`13)
RNA polymerase II holoenzyme wikipedia , lookup
Proteolysis wikipedia , lookup
Expression vector wikipedia , lookup
Eukaryotic transcription wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Transcription factor wikipedia , lookup
Point mutation wikipedia , lookup
Protein–protein interaction wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Paracrine signalling wikipedia , lookup
Gene expression wikipedia , lookup
Histone acetylation and deacetylation wikipedia , lookup
Two-hybrid screening wikipedia , lookup
Biochemistry wikipedia , lookup
Gene regulatory network wikipedia , lookup
Secreted frizzled-related protein 1 wikipedia , lookup
Endogenous retrovirus wikipedia , lookup
Promoter (genetics) wikipedia , lookup
SARAH PATRICE JUSTVIG The Effect of Small Molecule Inhibitor YK-4-279 on Activity of Transcription Factors in Prostate Cancer Dr. Heidi Elmendorf, Department of Biology, Georgetown University; Dr. Aykut Üren and Saïd Rahim, Department of Oncology, Department of Biochemistry and Molecular & Cellular Biology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center The ETS family of transcription factors is implicated in 40-70% of prostate cancers, including the most penetrating forms. Transcriptional regulator proteins ERG and ETV1 are members of the ETS family. EWS/FLI1, an oncogenic, chimeric fusion protein of Ewing’s sarcoma, shares with ERG and ETV1 identification as a Class I ETS factor. The three are more than 60% identical and 80% homologous in their amino acid sequences. YK-4-279 has been identified as a small molecule inhibitor of EWS/FLI1 oncoprotein in Ewing’s sarcoma. Given the strong similarity between EWS/FLI1 in Ewing’s sarcoma and ERG and ETV1 in prostate cancer, we hypothesized that YK-4-279 may inhibit ERG and ETV1 transcriptional activity. In an effort to determine the effect of YK-4-279 on ERG/ETV1 function with transcriptional activity as a readout, we chose ERG/ETV1-regulated target genes, optimized primer pairs, and performed qPCR to study relative gene expression of YK-4279 and DMSO groups both in vitro and in vivo. We utilized the human LNCaP cell line and subcutaneous xenografts, namely eight SCID mice, respectively. We found that YK4-279 significantly inhibited ERG/ETV1 function in MMP-7, FKBP10, and GLYATL2 target genes but that YK-4-279’s inhibition of ERG/ETV1 function in MMP-13 in vitro did not translate to the in vivo model. We are now extending our focus from a transcriptional level to a translational level through Western blotting, looking at YK-4279’s ability to affect protein levels. References Erkizan, H.V., Kong, Y., Merchant, M., Schlottmann, S., Barber-Rotenberg, J.S., Yuan, L., Abaan, O.D., Chou, T., Dakshanamurthy, S., Brown, M.L., Üren, A., and Toretsky, J.A. (2009) Nat. Med. 15(7):750-757. Rahim, S., Beauchamp, E.M., Kong, Y., Brown, M.L., Toretsky, J.A., and Üren, A. (2011) YK-4-279 Inhibits ERG and ETV1 Mediated Prostate Cancer Cell Invasion. PLOS ONE. 6(4):1-8.