A gene expression profile that defines colon cell maturation in vitro

John M. Mariadason, Diego Arango, Georgia A. Corner, Maria J. Arañes, Kylie A. Hotchkiss, Wancai Yang, Leonard H. Augenlicht

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Colonic epithelial cells undergo cell cycle arrest, lineage specific differentiation, and apoptosis, as they migrate along the crypt axis toward the lumenal surface. The Caco-2 colon carcinoma cell line models many of these phenotypic changes, in vitro. We used this model system and cDNA microarray analysis to characterize the genetic reprogramming that accompanies colon cell differentiation. The analyses revealed extensive yet functionally coordinated alterations in gene expression during the differentiation program. Consistent with cell differentiation reflecting a more specialized phenotype, the majority of changes (70%) were down-regulations of gene expression. Specifically, Caco-2 cell differentiation was accompanied by the coordinate down-regulation of genes involved in cell cycle progression and DNA synthesis, which reflected the concomitant reduction in cell proliferation. Simultaneously, genes involved in RNA splicing and transport, protein translation, folding, and degradation, were coordinately down-regulated, paralleled by a reduction in protein synthesis. Conversely, genes involved in xenobiotic and drug metabolism were up-regulated, which was linked to increased resistance of differentiated cells to chemotherapeutic agents. Increased expression of genes involved in extracellular matrix deposition, lipid transport, and lipid metabolism were also evident. Underlying these altered profiles of expression, components of signal transduction pathways, and several transcription factors were altered in expression.

Original languageEnglish (US)
Pages (from-to)4791-4804
Number of pages14
JournalCancer Research
Volume62
Issue number16
StatePublished - Aug 15 2002

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Transcriptome
Cell Differentiation
Colon
Down-Regulation
RNA Transport
Genes
RNA Splicing
Gene Expression
Caco-2 Cells
Protein Folding
Gene Expression Regulation
Protein Biosynthesis
Xenobiotics
Microarray Analysis
Cell Cycle Checkpoints
Oligonucleotide Array Sequence Analysis
Lipid Metabolism
Proteolysis
Extracellular Matrix
Signal Transduction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mariadason, J. M., Arango, D., Corner, G. A., Arañes, M. J., Hotchkiss, K. A., Yang, W., & Augenlicht, L. H. (2002). A gene expression profile that defines colon cell maturation in vitro. Cancer Research, 62(16), 4791-4804.

A gene expression profile that defines colon cell maturation in vitro. / Mariadason, John M.; Arango, Diego; Corner, Georgia A.; Arañes, Maria J.; Hotchkiss, Kylie A.; Yang, Wancai; Augenlicht, Leonard H.

In: Cancer Research, Vol. 62, No. 16, 15.08.2002, p. 4791-4804.

Research output: Contribution to journalArticle

Mariadason, JM, Arango, D, Corner, GA, Arañes, MJ, Hotchkiss, KA, Yang, W & Augenlicht, LH 2002, 'A gene expression profile that defines colon cell maturation in vitro', Cancer Research, vol. 62, no. 16, pp. 4791-4804.
Mariadason JM, Arango D, Corner GA, Arañes MJ, Hotchkiss KA, Yang W et al. A gene expression profile that defines colon cell maturation in vitro. Cancer Research. 2002 Aug 15;62(16):4791-4804.
Mariadason, John M. ; Arango, Diego ; Corner, Georgia A. ; Arañes, Maria J. ; Hotchkiss, Kylie A. ; Yang, Wancai ; Augenlicht, Leonard H. / A gene expression profile that defines colon cell maturation in vitro. In: Cancer Research. 2002 ; Vol. 62, No. 16. pp. 4791-4804.
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