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J Clin Invest. 2010 Dec;120(12):4179-82. doi: 10.1172/JCI45406. Epub 2010 Nov 22.

The RB tumor suppressor: a gatekeeper to hormone independence in prostate cancer?

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Ben May Department for Cancer Research, Gordon Center for Integrative Sciences, University of Chicago, Chicago, Illinois, USA.


The retinoblastoma tumor suppressor gene (RB1; encoding RB) is often cited as a gatekeeper, whose inactivation - direct or indirect - is a rate-limiting step for tumor initiation. However, in this issue of the JCI, Sharma et al. show that RB1 loss is a late event in human prostate cancer that is coincident with the emergence of castrate-resistant metastatic disease. This role for RB1 was linked to both E2F transcription factor 1-driven upregulation of the androgen receptor (AR) and increased recruitment of the AR to target gene promoters. This unexpected function for RB1 in late-stage cancer calls upon us to reassess the significance of RB1 inactivation in other cancers in terms of its timing, function in disease etiology, and relevance for cancer therapy.

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