Targeting ATF4 target genes for prostate cancer therapy
Our laboratory is studying proteins that are implicated in the progression of prostate cancer (PCa) and has previously identified a number of genes that are involved in this regard. Activating transcription factor 4 (ATF4) functions as a transcription factor that regulates genes to help the cell to adapt to the stress factors and plays an important role in PCa growth. Our in vitro experiments with both siRNA and shRNA showed that ATF4 is crucial for PCa cell growth and survival. We would now like to validate our results in vivo using preclinical prostate cancer models. By subcutaneously engrafting VCaP or 22RV1cells into nude mice, we will determine if loss of ATF4 prevents PCa cell growth in this model, too.
In addition, we have identified new ATF4 target genes that are crucial for the growth of PCa cells in vitro and represent promising therapeutic targets. We would now like to assess the ability of nanoliposomal siRNA directed against the new ATF4 target genes to target PCa tumors in vivo. We will subcutaneously engraft human PCa cell lines VCaP and 22RV1 into the flanks of nude mice and treat the mice with nanoliposomal siRNA bi-weekly. We will then determine if the loss of the new ATF4 target genes prevents PCa cell growth in vivo similar to what we have observed in vitro.
In addition, we have identified new ATF4 target genes that are crucial for the growth of PCa cells in vitro and represent promising therapeutic targets. We would now like to assess the ability of nanoliposomal siRNA directed against the new ATF4 target genes to target PCa tumors in vivo. We will subcutaneously engraft human PCa cell lines VCaP and 22RV1 into the flanks of nude mice and treat the mice with nanoliposomal siRNA bi-weekly. We will then determine if the loss of the new ATF4 target genes prevents PCa cell growth in vivo similar to what we have observed in vitro.