Prostate cancer originating in basal cells progresses to adenocarcinoma propagated by luminal-like cells

Tanya Stoyanova, Aaron R. Cooper, Justin M Drake, Xian Liu, Andrew J. Armstrong, Kenneth J. Pienta, Hong Zhang, Donald B. Kohn, Jiaoti Huang, Owen N. Witte, Andrew S. Goldstein

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89 Scopus citations

Abstract

The relationship between the cells that initiate cancer and the cancer stem-like cells that propagate tumors has been poorly defined. In a human prostate tissue transformation model, basal cells expressing the oncogenes Myc and myristoylated AKT can initiate heterogeneous tumors. Tumors contain features of acinartype adenocarcinoma with elevated eIF4E-driven protein translation and squamous cell carcinoma marked by activated betacatenin. Lentiviral integration site analysis revealed that alternative histological phenotypes can be clonally derived from a common cell of origin. In advanced disease, adenocarcinoma can be propagated by self-renewing tumor cells with an androgen receptor-low immature luminal phenotype in the absence of basal-like cells. These data indicate that advanced prostate adenocarcinoma initiated in basal cells can be maintained by luminal-like tumor-propagating cells. Determining the cells that maintain human prostate adenocarcinoma and the signaling pathways characterizing these tumor-propagating cells is critical for developing effective therapeutic strategies against this population.

Original languageEnglish (US)
Pages (from-to)20111-20116
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number50
DOIs
StatePublished - Dec 10 2013
Externally publishedYes

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    Stoyanova, T., Cooper, A. R., Drake, J. M., Liu, X., Armstrong, A. J., Pienta, K. J., Zhang, H., Kohn, D. B., Huang, J., Witte, O. N., & Goldstein, A. S. (2013). Prostate cancer originating in basal cells progresses to adenocarcinoma propagated by luminal-like cells. Proceedings of the National Academy of Sciences of the United States of America, 110(50), 20111-20116. https://doi.org/10.1073/pnas.1320565110