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

Published

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 2013

Published In

Volume / Issue

  • 110 / 50

Start / End Page

  • 20111 - 20116

PubMed ID

  • 24282295

Pubmed Central ID

  • 24282295

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1320565110

Language

  • eng