GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE72347 Query DataSets for GSE72347
Status Public on Jan 01, 2016
Title Molecular Characterization of Spontaneously Transformed Epithelial Murine Colon Cell Lines as a Model of Human Colorectal Neoplasia (expression)
Organism Mus musculus
Experiment type Expression profiling by array
Summary To characterize a series of mouse colon cells that have become spontaneously transformed over time in order to identify the chromosomal and genomic alterations that take place during the development of tumorigenesis.
Colorectal cancer is the third common malignancy in the United States. The stepwise progression from adenoma to carcinoma is accompanied by specific genomic alterations. Existing mouse models of human colon cancer have been induced by chemicals, viruses, or through genetic manipulation. Presented here is a unique mouse model of spontaneous transformation designed to identify the sequential steps of tumorigenesis. Normal epithelial colon cells were selectively isolated from the large intestine from eight different isogenic five-six week old C57BL/6 mice. Primary colon cells were grown in vitro with reduced serum concentration. The cells were sequentially recovered from culture based on distinct morphological changes: first, when the cells were in the pre-immortal stage and established as adherent cultures; second, as the cells bypassed crisis, increased their mitotic activity and became immortal; third, at early transformation, as the cells first formed foci; fourth, mid-transformed where the cells had higher proliferation rates in later passages; and finally, late transformed with rapid proliferation, contact inhibition, and multiple foci. The cells within each stage were analyzed using the molecular cytogenetic techniques of spectral karyotyping (SKY) and array comparative genomic hybridization (aCGH), and gene expression profiling. The late transformed cells were injected into nude mice to assess their tumorigenic potential. Spectral karyotyping revealed many recurrent structural and numerical aberrations, specifically in the late transformed cells. Loss of chromosome 4 is a consistent chromosomal aberration observed in all stages of the transformed colon cells, as well as in other tissues during the process of spontaneous transformation. Array CGH identified a pattern of gains and losses, and showed deletions of APC and Trp53 as well as a gain of Kras similar that observed in human colorectal cancer. Gene expression profiling identified the deregulation of several genes known to be involved in the progression of human colon cancer. Tumors resulted from three of the eight late transformed cultures confirming tumorigenic potential. Ultimately, the molecular characterization of spontaneously transformed murine epithelial colon cells indeed recapitulated the step wise progression of human colon cancer, and will prove to be an invaluable system in which to test potential rational intervention strategies.
Overall design Mouse colon epithelial cells were isolated from the colon of 8 isogenic C57BL\6 mice. These cells were grown in reduced serum and over time spontaneously became immortal and transformed. Our objective is to compare these changes to those that occur during human colon cancer development.
Contributor(s) McNeil NE, Padilla-Nash HM, Hu Y, Ried T
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Aug 25, 2015
Last update date Jan 12, 2017
Contact name Hesed Maria Padilla-Nash
Phone 301-435-4019
Organization name NCI
Department Genetics Branch
Lab Section of Cancer Genomics
Street address 50 South Drive
City Bethesda
State/province MD
ZIP/Postal code 20892-8010
Country USA
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (17)
GSM1860699 NCI-HPN-F3K Colon p3 PreImmortal
GSM1860700 NCI-HPN-F1K Colon p0 uncultured
GSM1860701 NCI-HPN-M1K Colon p5 PreImmortal
This SubSeries is part of SuperSeries:
GSE72349 Molecular Characterization of Spontaneously Transformed Epithelial Murine Colon Cell Lines as a Model of Human Colorectal Neoplasia
BioProject PRJNA293853

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE72347_RAW.tar 140.4 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap