Prostate epithelial cell of origin determines cancer differentiation state in an organoid transformation assay
Abstract
This study demonstrates that both primary human basal and luminal epithelial cells are cells of origin for prostate cancer through the use of a prostate organoid culture system. This technology enables the monitoring of early stages of prostate tumorigenesis in vitro and the interrogation of human prostate epithelial populations with synonymous oncogenic stimuli. The combination of c-Myc overexpression and activation of the PI3K/AKT pathway drives high-grade prostate adenocarcinoma in basal cell-derived tumors; however, the same oncogenic stress causes low-grade prostate adenocarcinoma in luminal cell-derived tumors. These findings indicate inherent context-specific and lineage-dependent differences in the response of human prostate epithelial cells to oncogenic stimuli.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 04, 2016
- Source ID
- 10.1073/pnas.1603645113
Entities
People
- Donghui Cheng
- Jiaoti Huang
- John K Lee
- John W. Phillips
- Jung Wook Park
- Owen N Witte
- Patrick Huang
Organizations
- American Association for Cancer Research
- Congressionally Directed Medical Research Programs
- Howard Hughes Medical Institute
- National Cancer Institute
- Prostate Cancer Foundation
- University of California
- University of California, Los Angeles