Epithelial Cell Organization Suppresses Myc Function by Attenuating Myc Expression

Simpson, D. R., Yu, M., Zheng, S. Y., Zhao, Z. M., Muthuswamy, S. K., Tansey, W. P. (June 2011) Epithelial Cell Organization Suppresses Myc Function by Attenuating Myc Expression. Cancer Research, 71 (11). pp. 3822-3830. ISSN 0008-5472

URL: http://www.ncbi.nlm.nih.gov/pubmed/21610111
DOI: 10.1158/0008-5472.CAN-10-3782

Abstract

c-Myc is an oncogene transcription factor that causes cancer in many settings, including solid tumors that arise in the context of organized tissue structures. Given that disruption of tissue architecture frequently occurs in cancer, there is considerable interest in how cell organization impacts oncogene function. A previous report found that organization of mammary epithelial cells into defined 3-dimensional structures renders them insensitive to the effects of retrovirus-mediated overexpression of Myc, leading to the notion that organization tempers the sensitivity of individual cells to Myc activity. In this article, we report that epithelial cell organization does not profoundly alter Myc activity but, instead, suppresses Myc by modulating its expression. We show that the morphogenesis of mammary epithelial cells into organized acinar structures in vitro is accompanied by widespread changes in gene expression patterns, including a substantial decrease in the expression of Myc. Concomitant with the decrease in endogenous Myc expression, we observe a decrease in transcription from retroviral vectors during morphogenesis and find that Myc transgene expression in acini is much lower than in unorganized cells. This decrease in Myc transgene activity is responsible for the apparent recalcitrance of organized cells to ectopic Myc, as adenovirus-mediated expression of Myc in organized structures potently induces apoptosis. These observations reveal that organization does not alter the inherent response of epithelial cells to Myc and suggest that other tumor suppression mechanisms, apart from structure, antagonize Myc in the development of solid tumors.

Item Type: Paper
Uncontrolled Keywords: c-myc breast-cancer essential cofactor lumen formation in-vivo polarity protein acini phosphorylation overexpression
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Myc
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > cell types and functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
CSHL Authors:
Communities: CSHL labs > Muthuswamy lab
CSHL labs > Tansey lab
Watson School > Publications
CSHL Cancer Center Program > Signal Transduction
Depositing User: Matt Covey
Date: June 2011
Date Deposited: 05 Feb 2013 15:53
Last Modified: 16 Oct 2015 15:38
PMCID: PMC3347713
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27200

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