Prostate cancer originating in basal cells progresses to adenocarcinoma propagated by luminal-like cells.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Stoyanova, T; Cooper, AR; Drake, JM; Liu, X; Armstrong, AJ; Pienta, KJ; Zhang, H; Kohn, DB; Huang, J; Witte, ON; Goldstein, AS
Published Date
- December 10, 2013
Published In
Volume / Issue
- 110 / 50
Start / End Page
- 20111 - 20116
PubMed ID
- 24282295
Pubmed Central ID
- PMC3864278
Electronic International Standard Serial Number (EISSN)
- 1091-6490
Digital Object Identifier (DOI)
- 10.1073/pnas.1320565110
Language
- eng
Conference Location
- United States