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注册报告:雄激素受体在男性去势抵抗性前列腺癌中诱导独特的转录程序。

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

作者信息

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

机构信息

Noble Life Sciences, Inc. , Gaithersburg, MD , USA.

Science Exchange and The Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative , Palo Alto, CA , USA.

出版信息

PeerJ. 2015 Sep 15;3:e1231. doi: 10.7717/peerj.1231. eCollection 2015.

DOI:10.7717/peerj.1231
PMID:26401447
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4579027/
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.

摘要

前列腺癌基金会-胡子月基金会可重复性倡议(PCFMFRI)旨在通过对前列腺癌领域近期论文进行重复实验,来应对科学界对研究可重复性日益增长的担忧。本注册报告描述了对夏尔马及其同事于2013年发表在《癌细胞》杂志上的论文《雄激素受体在去势抵抗性前列腺癌患者中诱导独特的转录程序》中的关键实验所提出的重复计划。在雄激素受体(AR)的数千个靶点中,作者阐明了一组16个核心基因,这些基因在去势后持续下调,并在去势抵抗时重新出现。这16个AR结合位点与在培养细胞中观察到的不同。作者认为细胞环境可能对AR结合位点的下游转录调控产生显著影响。本研究将通过比较夏尔马及其同事在异种移植肿瘤组织中鉴定出的16个核心基因的基因表达与体外雄激素处理的LNCaP细胞中的基因表达,来尝试重复图7C。前列腺癌基金会-胡子月基金会可重复性倡议是前列腺癌基金会、胡子月倡议和科学交流公司之间的合作,重复实验的结果将由PeerJ发表。

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本文引用的文献

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The association of XRCC3 Thr241Met genetic variant with risk of prostate cancer: a meta-analysis.XRCC3基因Thr241Met变异与前列腺癌风险的关联:一项荟萃分析。
Afr Health Sci. 2015 Mar;15(1):117-22. doi: 10.4314/ahs.v15i1.16.
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A molecular analysis provides novel insights into androgen receptor signalling in breast cancer.分子分析为乳腺癌中雄激素受体信号传导提供了新的见解。
PLoS One. 2015 Mar 17;10(3):e0120622. doi: 10.1371/journal.pone.0120622. eCollection 2015.
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The biology of castration-resistant prostate cancer.去势抵抗性前列腺癌的生物学
Curr Probl Cancer. 2015 Jan-Feb;39(1):17-28. doi: 10.1016/j.currproblcancer.2014.11.004. Epub 2014 Nov 25.
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Anterior gradient 2 downregulation in a subset of pancreatic ductal adenocarcinoma is a prognostic factor indicative of epithelial-mesenchymal transition.前梯度 2 在一部分胰腺导管腺癌中下调,是预示上皮-间充质转化的预后因素。
Lab Invest. 2015 Feb;95(2):193-206. doi: 10.1038/labinvest.2014.138. Epub 2014 Nov 24.
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TM4SF4 overexpression in radiation-resistant lung carcinoma cells activates IGF1R via elevation of IGF1.耐辐射肺癌细胞中TM4SF4的过表达通过升高IGF1来激活IGF1R。
Oncotarget. 2014 Oct 30;5(20):9823-37. doi: 10.18632/oncotarget.2450.
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Molecular pathways and targets in prostate cancer.前列腺癌中的分子途径与靶点
Oncotarget. 2014 Sep 15;5(17):7217-59. doi: 10.18632/oncotarget.2406.
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Splice variant transcripts of the anterior gradient 2 gene as a marker of prostate cancer.前梯度2基因的剪接变异转录本作为前列腺癌的标志物
Oncotarget. 2014 Sep 30;5(18):8681-9. doi: 10.18632/oncotarget.2365.
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TM4SF1: a new vascular therapeutic target in cancer.TM4SF1:癌症中的一种新的血管治疗靶点。
Angiogenesis. 2014 Oct;17(4):897-907. doi: 10.1007/s10456-014-9437-2. Epub 2014 Jul 2.
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Biologic and clinical significance of androgen receptor variants in castration resistant prostate cancer.去势抵抗性前列腺癌中雄激素受体变体的生物学及临床意义
Endocr Relat Cancer. 2014 Aug;21(4):T87-T103. doi: 10.1530/ERC-13-0470. Epub 2014 May 23.