# Registered report: the androgen receptor induces a distinct transcriptional program in castration-resistant prostate cancer in man

**Authors:** Denise Chronscinski, Srujana Cherukeri, Fraser Tan, Nicole Perfito, Joelle Lomax, Elizabeth Iorns

PMC · DOI: 10.7717/peerj.1231 · PeerJ · 2015-09-15

## TL;DR

This study aims to replicate findings from a 2013 paper showing how the androgen receptor affects gene expression in prostate cancer that resists castration.

## Contribution

The study contributes by attempting to reproduce key results on AR-induced gene expression in prostate cancer xenografts.

## Key findings

- The original study identified 16 core genes downregulated with castration and re-emerged with resistance.
- AR binding sites in xenografts were distinct from those in cultured cells.
- The replication aims to confirm these findings in a different experimental setup.

## Abstract

The Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative (PCFMFRI) seeks to address growing concerns about reproducibility in scientific research by conducting replications of recent papers in the field of prostate cancer. This Registered Report describes the proposed replication plan of key experiments from “The Androgen Receptor Induces a Distinct Transcriptional Program in Castration-Resistant Prostate Cancer in Man” by Sharma and colleagues (2013), 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 downregulated 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 Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative is a collaboration between the Prostate Cancer Foundation, the Movember Initiative, and Science Exchange, and the results of the replications will be published by PeerJ.

## Linked entities

- **Genes:** AR (androgen receptor) [NCBI Gene 367]
- **Diseases:** prostate cancer (MONDO:0005159)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** TM4SF5 (transmembrane 4 L six family member 5) [NCBI Gene 9032], AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, TNFSF10 (TNF superfamily member 10) [NCBI Gene 8743] {aka APO2L, Apo-2L, CD253, TANCR, TL2, TNLG6A}, TSPAN13 (tetraspanin 13) [NCBI Gene 27075] {aka NET-6, NET6, TM4SF13}, EIF2B5 (eukaryotic translation initiation factor 2B subunit epsilon) [NCBI Gene 8893] {aka CACH, CLE, EIF-2B, EIF2Bepsilon, LVWM, VWM5}, MAD1L1 (mitotic arrest deficient 1 like 1) [NCBI Gene 8379] {aka MAD1, MVA7, PIG9, TP53I9, TXBP181}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, SEC61A1 (SEC61 translocon subunit alpha 1) [NCBI Gene 29927] {aka ADTKD5, CVID15, HNFJ4, HSEC61, SEC61, SEC61A}, NT5DC3 (5'-nucleotidase domain containing 3) [NCBI Gene 51559] {aka TU12B1-TY, TU12B1TY}, TYW2 (tRNA wybutosine-synthesizing protein 2) [NCBI Gene 55039] {aka TRM12, TRMT12}, ABHD12 (abhydrolase domain containing 12, lysophospholipase) [NCBI Gene 26090] {aka ABHD12A, BEM46L2, C20orf22, PHARC, dJ965G21.2, hABHD12}, XRCC3 (X-ray repair cross complementing 3) [NCBI Gene 7517] {aka CMM6}, STIL (STIL centriolar assembly protein) [NCBI Gene 6491] {aka MCPH7, SIL}, ECI2 (enoyl-CoA delta isomerase 2) [NCBI Gene 10455] {aka ACBD2, DRS-1, DRS1, HCA88, PECI, dJ1013A10.3}, AGR2 (anterior gradient 2, protein disulphide isomerase family member) [NCBI Gene 10551] {aka AG-2, AG2, GOB-4, HAG-2, HEL-S-116, HPC8}, TM4SF1 (transmembrane 4 L six family member 1) [NCBI Gene 4071] {aka H-L6, L6, M3S1, TAAL6}, Camkk2 (calcium/calmodulin-dependent protein kinase kinase 2, beta) [NCBI Gene 207565] {aka 6330570N16Rik, mKIAA0787}, Fdxr (ferredoxin reductase) [NCBI Gene 14149] {aka AR}, SLC26A2 (solute carrier family 26 member 2) [NCBI Gene 1836] {aka D5S1708, DTD, DTDST, EDM4, MST153, MSTP157}, GFM1 (G elongation factor mitochondrial 1) [NCBI Gene 85476] {aka COXPD1, EFG, EFG1, EFGM, EGF1, GFM}, NDUFB11 (NADH:ubiquinone oxidoreductase subunit B11) [NCBI Gene 54539] {aka CI-ESSS, ESSS, MC1DN30, NP17.3, Np15, P17.3}
- **Diseases:** Cancer (MESH:D009369), PC (MESH:D011471), lung adenocarcinoma (MESH:D000077192), deaths (MESH:D003643), breast cancer (MESH:D001943), pancreatic ductal adenocarcinoma (MESH:D021441), benign prostate hyperplasia (MESH:D011470), CRPC (MESH:D064129), mycoplasma (MESH:D009175)
- **Chemicals:** Isoflurane (MESH:D007530), TRIzol (MESH:C411644), F4135 (-), steroid (MESH:D013256), insulin (MESH:D007328), bacitracin zinc (MESH:D001414), Silicon-carbide (MESH:C022088), neomycin sulfate (MESH:D009355), nitrogen (MESH:D009584), PBS (MESH:D007854), DMSO (MESH:D004121), Buprenorphin (MESH:D002047), Isopropanol (MESH:D019840), R1881 (MESH:D015741), SYBR Green (MESH:C098022), CO2 (MESH:D002245), Phenol-red (MESH:D010637), Ketamine (MESH:D007649), Xylazine (MESH:D014991)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** Thr241Met
- **Cell lines:** LNCaP — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0395), FGC — Rattus norvegicus (Rat), Rat hepatocellular carcinoma, Cancer cell line (CVCL_0261), NOD — Mus musculus (Mouse), Induced pluripotent stem cell (CVCL_B3R1)

## Full text

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## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC4579027/full.md

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Source: https://tomesphere.com/paper/PMC4579027