Cancers are distributed unevenly across the body, but the importance of cell intrinsic factors such as stem cell function in determining organ cancer risk is unknown. Therefore, we used Cre-recombination of conditional lineage tracing, oncogene, and tumor suppressor alleles to define populations of stem and non-stem cells in mouse organs and test their life-long susceptibility to tumorigenesis. We show that tumor incidence is determined by the life-long generative capacity of mutated cells. This relationship held true in the presence of multiple genotypes and regardless of developmental stage, strongly supporting the notion that stem cells dictate organ cancer risk. Using the liver as a model system, we further show that damage-induced activation of stem cell function markedly increases cancer risk. Therefore, we propose that a combination of stem cell mutagenesis and extrinsic factors that enhance the proliferation of these cell populations, creates a "perfect storm" that ultimately determines organ cancer risk. VIDEO ABSTRACT.
Pubmed ID: 27565343 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A portal that provides visualization, analysis and download of large-scale cancer genomics data sets.
View all literature mentionsThis unknown targets
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets Generated from formalin fixed human liver
View all literature mentionsThis polyclonal targets Mouse Sall4
View all literature mentionsThis polyclonal targets GLUL
View all literature mentionsThis monoclonal targets Catenin, beta
View all literature mentionsThis monoclonal targets Human HNF-4 alpha / NR2A1 (Isoforms 1-6)
View all literature mentionsThis monoclonal targets Cytokeratin 19 antibody [EPNCIR127B]
View all literature mentionsThis polyclonal targets Androgen Receptor antibody produced in rabbit
View all literature mentionsThis unknown targets phospho-Histone H3 (Ser10)
View all literature mentionsMus musculus with name STOCK Gt(ROSA)26Sortm1(Notch1)Dam/J from IMSR.
View all literature mentionsMus musculus with name B6N;129S-Prom1tm1(cre/ERT2)Gilb/J from IMSR.
View all literature mentionsMus musculus with name C;129S4-Ptentm1Hwu/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2-Trp53tm1Brn/J from IMSR.
View all literature mentionsMus musculus with name B6.129S1-Cdkn2atm4Cjs/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm6(CAG-ZsGreen1)Hze/J from IMSR.
View all literature mentionsSoftware R package for fitting generalized linear mixed models (GLMMs) using AD Model Builder. Fits mixed-effects models to count data using Poisson or negative binomial response distributions.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsA comprehensive suite of advanced statistics and interactive data visualization specifically designed to reliably extract biological signals from noisy data.
View all literature mentionsImaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
View all literature mentionsMus musculus with name B6.129-Krastm4Tyj/Nci from IMSR.
View all literature mentionsMus musculus with name B6.129S1-Cdkn2atm4Cjs/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2-Trp53tm1Brn/J from IMSR.
View all literature mentionsMus musculus with name C;129S4-Ptentm1Hwu/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm6(CAG-ZsGreen1)Hze/J from IMSR.
View all literature mentionsMus musculus with name B6N;129S-Prom1tm1(cre/ERT2)Gilb/J from IMSR.
View all literature mentionsMus musculus with name STOCK Gt(ROSA)26Sortm1(Notch1)Dam/J from IMSR.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsMus musculus with name B6.129-Krastm4Tyj/Nci from IMSR.
View all literature mentionsMus musculus with name B6.129S1-Cdkn2atm4Cjs/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2-Trp53tm1Brn/J from IMSR.
View all literature mentionsMus musculus with name C;129S4-Ptentm1Hwu/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm6(CAG-ZsGreen1)Hze/J from IMSR.
View all literature mentionsMus musculus with name STOCK Gt(ROSA)26Sortm1(Notch1)Dam/J from IMSR.
View all literature mentionsMus musculus with name B6N;129S-Prom1tm1(cre/ERT2)Gilb/J from IMSR.
View all literature mentions