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Volume 15, Issue 3 (May 2013) 15, 328–332; 10.1038/aja.2013.7
Neuroendocrine differentiation of prostate cancer
Zhen Li, Clark J Chen, Jason K Wang, Elaine Hsia, Wei Li, Jill Squires, Yin Sun and Jiaoti Huang
Departments of Pathology and Urology, Jonsson Comprehensive Cancer Center and Broad Center for Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095–1732, USA
Correspondence: Dr J Huang, (JiaotiHuang@mednet.ucla.edu)
Received 30 November 2012; Revised 8 January 2013; Accepted 9 January 2013; Advance online publication 18 March 2013
| Abstract |
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Benign prostate and prostatic adenocarcinoma contain rare quiescent neuroendocrine cells while small cell neuroendocrine carcinoma (SCNC), a variant form of prostate cancer, contains highly proliferative neuroendocrine tumor cells. We provide evidence that IL-8-CXCR2-P53 pathway keeps the NE cells in a quiescent state normally. P53 mutation inactivates this pathway, resulting in hyper-proliferation and aggressive behavior of the NE cells in SCNC. Therefore, we have identified potential cells of origin and a molecular target for prostatic SCNC that are different from those of adenocarcinoma, which explains SCNC′s distinct biology and the clinical observation that it does not respond to hormonal therapy.
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