Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in DNA sequestration as measured by AluI restriction enzyme.

Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in DNA sequestration as measured by AluI restriction enzyme. Research Abstract Details 

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Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in DNA sequestration as measured by AluI restriction enzyme. Abstract Text:

Eleni Papadopulos-Eleopulos,Barry A P Page,David Causer,Valendar F Turner,John M Papadimitriou,Eleni Papadopulos-Eleopulos,Barry A P Page,David Causer,Valendar F Turner,John M Papadimitriou,

The importance of microenvironment and context in regulation of tissue-specific genes is well established. DNA exposure to or the sequestration from nucleases detects differences in higher order chromatin structure in intact cells without disturbing cellular or tissue architecture. To investigate the relationship between chromatin organization and tumor phenotype, we used an established three-dimensional assay in which normal and malignant human breast cells can be easily distinguished by the morphology of the structures they make (acinus-like versus tumor-like, respectively). We show that these phenotypes can be distinguished also by sensitivity to AluI digestion in which the malignant cells resist digestion relative to nonmalignant cells. Treatment of T4-2 breast cancer cells in three-dimensional culture with cAMP analogs or a phosphatidylinositol 3-kinase inhibitor not only reverted their phenotype from nonpolar to polar acinar-like structures but also enhanced chromatin sensitivity to AluI. By using different cAMP analogs, we show that cAMP-induced phenotypic reversion, polarization, and shift in DNA organization act through a cAMP-dependent protein-kinase A-coupled signaling pathway. Importantly, inhibitory antibody to fibronectin produced the same effect. These experiments underscore the concept that modifying the tumor microenvironment can alter the organization of tumor cells and demonstrate that architecture and global chromatin organization are coupled and highly plastic.

Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in DNA sequestration as measured by AluI restriction enzyme. Publishing Authors By Initials

E Papadopulos-Eleopulos,BA Page,D Causer,VF Turner,JM Papadimitriou,E Papadopulos-Eleopulos,BA Page,D Causer,VF Turner,JM Papadimitriou,

For similar genetic phenomena: phenotype research abstracts see: genetic phenomena: phenotype research

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Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in DNA sequestration as measured by AluI restriction enzyme. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The American journal of pathology

VOLUME: 170

Page Numbers: 1739-49

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ISSN: 0002-9440

DAY: 3

MONTH: May

YEAR: 2007

Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in DNA sequestration as measured by AluI restriction enzyme. Information

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LANGUAGE: eng

NlmUniqueID: 370502

Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in DNA sequestration as measured by AluI restriction enzyme. Keywords Mesh Terms:

KEYWORDS: Phenotype

MESH TERMS: genetics

Chemical & Substance for Abstract: Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in DNA sequestration as measured by AluI restriction enzyme. Information

Substance Name: DNA Restriction Enzymes

Registry Number: EC 3.1.21.-

Grant and Affiliation Information for Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in DNA sequestration as measured by AluI restriction enzyme.

AFFILIATION: Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., 130 CSN (MC 847), Chicago, IL 60612, USA.

Country: United States

AGENCY: United States NEI

GRANT: EY10457

ACRONYM: EY

MEDLINETA: Am J Pathol

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