Prostate cancer originating in basal cells progresses to adenocarcinoma propagated by luminal-like cells
- 26 November 2013
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 110 (50), 20111-20116
- https://doi.org/10.1073/pnas.1320565110
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 acinar-type adenocarcinoma with elevated eIF4E-driven protein translation and squamous cell carcinoma marked by activated beta-catenin. 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.Keywords
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