Cellular mechanisms of risk and transformation

Leonard H. Augenlicht, Michael Bordonaro, Barbara G. Heerdt, John Mariadason, Anna Velcich

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Our early work using the first array and imaging methods for the quantitative analysis of the expression of 4000 cDNA sequences suggested that modulation of mitochondrial gene expression was a factor in determining whether colonic epithelial cells displayed a differentiated or transformed phenotype. We have since dissected a pathway in which mitochondrial function is a key element in determining the probability of cells undergoing cell cycle arrest, lineage-specific differentiation, and cell death. Moreover, this pathway is linked to signaling through β-catenin-Tcf, but in a manner that is independent of effects of the APC gene on β-catenin-Tcf activity. Utilization of unique mouse genetic models of intestinal tumorigenesis has confirmed that mitochondrial function is an important element in generation of apoptotic cells in the colon in vivo and has demonstrated that modulation of cell death may be involved in intestinal tumor progression rather than initiation. Normal spatial and temporal patterns of cell proliferation, differentiation, and apoptosis in the colonic mucosa are determined by developmentally programmed genetic signals and external signals generated by homo- and heterotypic cell interactions, humoral agents, and lumenal contents. Mitochondrial function may play a pivotal role in integrating these signals and in determining probability of cells entering different maturation pathways. Now this is accomplished is under investigation using high-density cDNA microarrays.

Original languageEnglish (US)
Pages (from-to)20-31
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume889
StatePublished - 1999

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Catenins
Cell death
Cell Death
Complementary DNA
Cells
Modulation
APC Genes
Mitochondrial Genes
Genetic Models
Cell proliferation
Microarrays
Cell Cycle Checkpoints
Oligonucleotide Array Sequence Analysis
Gene expression
Cell Communication
Tumors
Cell Differentiation
Colon
Carcinogenesis
Mucous Membrane

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Augenlicht, L. H., Bordonaro, M., Heerdt, B. G., Mariadason, J., & Velcich, A. (1999). Cellular mechanisms of risk and transformation. Annals of the New York Academy of Sciences, 889, 20-31.

Cellular mechanisms of risk and transformation. / Augenlicht, Leonard H.; Bordonaro, Michael; Heerdt, Barbara G.; Mariadason, John; Velcich, Anna.

In: Annals of the New York Academy of Sciences, Vol. 889, 1999, p. 20-31.

Research output: Contribution to journalArticle

Augenlicht, LH, Bordonaro, M, Heerdt, BG, Mariadason, J & Velcich, A 1999, 'Cellular mechanisms of risk and transformation', Annals of the New York Academy of Sciences, vol. 889, pp. 20-31.
Augenlicht LH, Bordonaro M, Heerdt BG, Mariadason J, Velcich A. Cellular mechanisms of risk and transformation. Annals of the New York Academy of Sciences. 1999;889:20-31.
Augenlicht, Leonard H. ; Bordonaro, Michael ; Heerdt, Barbara G. ; Mariadason, John ; Velcich, Anna. / Cellular mechanisms of risk and transformation. In: Annals of the New York Academy of Sciences. 1999 ; Vol. 889. pp. 20-31.
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