title: Prostate cancer originating in basal cells progresses to adenocarcinoma propagated by luminal-like cells.
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.
authors.affiliation: Microbiology, Immunology and Molecular Genetics, Molecular Biology Interdepartmental Ph.D. Program, Departments of Molecular and Medical Pharmacology, Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Howard Hughes Medical Institute, and Department of Urology, University of California, Los Angeles, CA 90095.
authors.forename: Tanya
authors.initials: T
authors.lastname: Stoyanova
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Cooper
authors.forename: Justin M
authors.initials: JM
authors.lastname: Drake
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Donald B
authors.initials: DB
authors.lastname: Kohn
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Goldstein
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology*; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018295:Neoplasms, Basal Cell / Q000503:physiopathology*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D051176:beta Catenin