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

Research output: Contribution to journalArticle

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

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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