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

2013; National Academy of Sciences; Volume: 110; Issue: 50 Linguagem: Inglês

10.1073/pnas.1320565110

1091-6490

Tanya Stoyanova, Aaron 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,

Cancer Cells and Metastasis

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.