Identification of a cell of origin for human prostate cancer

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) Vol. 329; no. 5991; p. 568
Main Authors: Goldstein, Andrew S, Huang, Jiaoti, Guo, Changyong, Garraway, Isla P, Witte, Owen N
Format: Journal Article
Language:English
Published: United States 30.07.2010
Subjects:
Animals
Biomarkers, Tumor - metabolism
Cell Separation
Cell Transformation, Neoplastic
Epithelial Cells - metabolism
Epithelial Cells - pathology
Epithelium - pathology
Flow Cytometry
Humans
Keratins - analysis
Male
Mice
Mice, Inbred NOD
Mice, SCID
Prostate - cytology
Prostate - metabolism
Prostate - pathology
Prostatic Intraepithelial Neoplasia - metabolism
Prostatic Intraepithelial Neoplasia - pathology
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Proto-Oncogene Proteins c-akt - metabolism
Receptors, Androgen - metabolism
Trans-Activators - metabolism
Transcriptional Regulator ERG
Transduction, Genetic
ISSN:1095-9203, 1095-9203
Online Access:Get more information
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Summary: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.
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.1189992