Stem cell models for functional validation of prostate cancer genes

Lindsey Ulkus, Min Wu, Scott D. Cramer

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Prostate cancer is a genomically complex disease in which initiation, progression, and metastasis are regulated by numerous molecular processes including oncogene activation or tumor suppressor inactivation. Understanding the molecular mechanisms that drive prostate tumorigenesis has important clinical implications. Putative oncogenes or tumor suppressors are identified using technologies including SNP arrays, microarrays, and whole genome sequencing, but these targets must then be evaluated in cell and animal models to determine the functional consequences of these genomic alterations. Traditionally, potential prostate cancer genes have been validated with human prostate cancer cell line models (i.e., tissue culture and xenograft systems) or genetically engineered mouse (GEM) models. More recently, stem cell models have been utilized to evaluate candidate cancer genes. Because the normal adult prostate stem cell (PSC) shares many properties with the prostate tumor-initiating cell (TIC) including the capabilities for self-renewal, differentiation, and androgen independence, modeling gene alterations in PSCs may be more appropriate than traditional approaches. PSCs can be maintained in cell culture, genetically manipulated, and characterized using techniques including cell sorting, colony formation assays, and prostasphere assays in vitro and tissue recombination in vivo. A number of prostatic oncogenes and tumor suppressors including MYC, ERG, PTEN, P53, NKX3.1, and TAK1 have been evaluated using stem cell models. Compound genetic alterations have also been studied using PSC models. In this chapter we describe current approaches being used to investigate putative oncogenes and tumor suppressors in the context of the PSC and highlight a few examples of recent studies using stem cell models for target validation. We also discuss the limitations of existing models as well as strategies to improve upon these models for future studies.

Original languageEnglish (US)
Title of host publicationStem Cells and Prostate Cancer
PublisherSpringer New York
Pages149-173
Number of pages25
ISBN (Electronic)9781461464983
ISBN (Print)1461464978, 9781461464976
DOIs
StatePublished - Dec 1 2013

ASJC Scopus subject areas

  • General Medicine

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