Identification of a Cell of Origin for Human Prostate Cancer -- Goldstein et al. 329 (5991): 568 -- Science

Science 30 July 2010:
Vol. 329. no. 5991, pp. 568 - 571
DOI: 10.1126/science.1189992

Reports
Identification of a Cell of Origin for Human Prostate Cancer
Andrew S. Goldstein,1 Jiaoti Huang,2,3,6 Changyong Guo,2,4 Isla P. Garraway,2,4 Owen N. Witte1,5,6,*

Luminal cells are believed to be the cells of origin for human prostate cancer, because the disease is characterized by luminal cell expansion and the absence of basal cells. Yet functional studies addressing the origin of human prostate cancer have not previously been reported because of a lack of relevant in vivo human models. Here we show that basal cells from primary benign human prostate tissue can initiate prostate cancer in immunodeficient mice. The cooperative effects of AKT, ERG, and androgen receptor in basal cells recapitulated the histological and molecular features of human prostate cancer, with loss of basal cells and expansion of luminal cells expressing prostate-specific antigen and alpha-methylacyl-CoA racemase. Our results demonstrate that histological characterization of cancers does not necessarily correlate with the cellular origins of the disease.

1 Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
2 Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
3 Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA 90095, USA.
4 Department of Urology, UCLA, Los Angeles, CA 90095, USA.
5 Department of Microbiology, Immunology and Molecular Genetics; Department of Molecular and Medical Pharmacology; Howard Hughes Medical Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
6 Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA.

* To whom correspondence should be addressed at Howard Hughes Medical Institute, UCLA, Los Angeles, 675 Charles E. Young Drive South, 5-748 MRL, Los Angeles, CA90095–1662, USA. E-mail: owenwitte@mednet.ucla.edu

Identification of a Cell of Origin for Human Prostate Cancer -- Goldstein et al. 329 (5991): 568 -- Science