Science Exchange published two papers in PeerJ, the online journal, that are being funded by the Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative. This initiative seeks to address growing concerns about reproducibility in scientific research by conducting replications of recent papers in the field of prostate cancer. It is a collaboration between the Prostate Cancer Foundation, the Movember Initiative, and Science Exchange. These two papers represent the first step to reproducing the original experiments. Today’s papers are meant to report what the collaborators will do so the scientific community has a full understanding of the process. PeerJ will publish the final results of the replications.
The first paper, The Androgen Receptor Induces a Distinct Transcriptional Program in Castration-Resistant Prostate Cancer in Man by Sharma and colleagues, was originally published in Cancer Cell in 2013. Of thousands of targets for the androgen receptor (AR), the authors elucidated a subset of 16 core genes that were consistently down-regulated with castration and re-emerged with castration resistance. These 16 AR binding sites were distinct from those observed in cells in culture. The authors suggested that cellular context can have dramatic effects on downstream transcriptional regulation of AR binding sites. The present study will attempt to replicate Fig. 7C by comparing gene expression of the 16 core genes identified by Sharma and colleagues in xenograft tumor tissue compared to androgen treated LNCaP cells in vitro.
The second paper Androgen Receptor Splice Variants Determine Taxane Sensitivity in Prostate Cancer by Thadani-Mulero and colleagues was published in Cancer Research in 2014. The experiment that will be replicated is reported in Fig. 6A. Thadani-Mulero and colleagues generated xenografts from two prostate cancer cell lines; LuCaP 86.2, which expresses predominantly the ARv567 splice variant of the androgen receptor (AR), and LuCaP 23.1, which expresses the full length AR as well as the ARv7 variant. Treatment of the tumors with the taxane docetaxel showed that the drug inhibited tumor growth of the LuCaP 86.2 cells but not of the LuCaP 23.1 cells, indicating that expression of splice variants of the AR can affect sensitivity to docetaxel.
Labs listed on Science Exchange will perform the lab work. These labs include Nobel Life Sciences, ProNovus Bioscience LLC, and the Stem Cell and Xenograft Core at the University of Pennsylvania.