Epigenetic silencing of DSC3 is a common event in human breast cancer

Persistent Link:
http://hdl.handle.net/10150/610111
Title:
Epigenetic silencing of DSC3 is a common event in human breast cancer
Author:
Oshiro, Marc; Kim, Christina; Wozniak, Ryan; Junk, Damian; Munoz-Rodriguez, Jose; Burr, Jeanne; Fitzgerald, Matthew; Pawar, Sangita; Cress, Anne; Domann, Frederick; Futscher, Bernard
Affiliation:
Departments of Pharmacology and Toxicology, Arizona Cancer Center, University of Arizona, Tucson, AZ, USA; Department of Surgery, Arizona Cancer Center, University of Arizona, Tucson, AZ, USA; Department of Cell Biology and Anatomy, Arizona Cancer Center, University of Arizona, Tucson, AZ, USA; Department of Radiation Oncology, Free Radical and Radiation Biology Program, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA
Issue Date:
2005
Publisher:
BioMed Central
Citation:
Breast Cancer Research 2005, 7:R669-R680 (DOI 10.1186/bcr1273)
Journal:
Breast Cancer Research
Rights:
© 2005 Oshiro et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
INTRODUCTION:Desmocollin 3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and a principle component of desmosomes. Desmosomal proteins such as DSC3 are integral to the maintenance of tissue architecture and the loss of these components leads to a lack of adhesion and a gain of cellular mobility. DSC3 expression is down-regulated in breast cancer cell lines and primary breast tumors; however, the loss of DSC3 is not due to gene deletion or gross rearrangement of the gene. In this study, we examined the prevalence of epigenetic silencing of DSC3 gene expression in primary breast tumor specimens.METHODS:We used bisulfite genomic sequencing to analyze the methylation state of the DSC3 promoter region from 32 primary breast tumor specimens. We also used a quantitative real-time RT-PCR approach, and analyzed all breast tumor specimens for DSC3 expression. Finally, in addition to bisulfite sequencing and RT-PCR, we used an in vivo nuclease accessibility assay to determine the chromatin architecture of the CpG island region from DSC3-negative breast cancer cells lines.RESULTS:DSC3 expression was downregulated in 23 of 32 (72%) breast cancer specimens comprising: 22 invasive ductal carcinomas, 7 invasive lobular breast carcinomas, 2 invasive ductal carcinomas that metastasized to the lymph node, and a mucoid ductal carcinoma. Of the 23 specimens showing a loss of DSC3 expression, 13 (56%) were associated with cytosine hypermethylation of the promoter region. Furthermore, DSC3 expression is limited to cells of epithelial origin and its expression of mRNA and protein is lost in a high proportion of breast tumor cell lines (79%). Lastly, DNA hypermethylation of the DSC3 promoter is highly correlated with a closed chromatin structure.CONCLUSION:These results indicate that the loss of DSC3 expression is a common event in primary breast tumor specimens, and that DSC3 gene silencing in breast tumors is frequently linked to aberrant cytosine methylation and concomitant changes in chromatin structure.
EISSN:
1465-542X
DOI:
10.1186/bcr1273
Version:
Final published version
Additional Links:
http://breast-cancer-research.com/content/7/5/R669

Full metadata record

DC FieldValue Language
dc.contributor.authorOshiro, Marcen
dc.contributor.authorKim, Christinaen
dc.contributor.authorWozniak, Ryanen
dc.contributor.authorJunk, Damianen
dc.contributor.authorMunoz-Rodriguez, Joseen
dc.contributor.authorBurr, Jeanneen
dc.contributor.authorFitzgerald, Matthewen
dc.contributor.authorPawar, Sangitaen
dc.contributor.authorCress, Anneen
dc.contributor.authorDomann, Fredericken
dc.contributor.authorFutscher, Bernarden
dc.date.accessioned2016-05-20T08:58:50Z-
dc.date.available2016-05-20T08:58:50Z-
dc.date.issued2005en
dc.identifier.citationBreast Cancer Research 2005, 7:R669-R680 (DOI 10.1186/bcr1273)en
dc.identifier.doi10.1186/bcr1273en
dc.identifier.urihttp://hdl.handle.net/10150/610111-
dc.description.abstractINTRODUCTION:Desmocollin 3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and a principle component of desmosomes. Desmosomal proteins such as DSC3 are integral to the maintenance of tissue architecture and the loss of these components leads to a lack of adhesion and a gain of cellular mobility. DSC3 expression is down-regulated in breast cancer cell lines and primary breast tumorsen
dc.description.abstracthowever, the loss of DSC3 is not due to gene deletion or gross rearrangement of the gene. In this study, we examined the prevalence of epigenetic silencing of DSC3 gene expression in primary breast tumor specimens.METHODS:We used bisulfite genomic sequencing to analyze the methylation state of the DSC3 promoter region from 32 primary breast tumor specimens. We also used a quantitative real-time RT-PCR approach, and analyzed all breast tumor specimens for DSC3 expression. Finally, in addition to bisulfite sequencing and RT-PCR, we used an in vivo nuclease accessibility assay to determine the chromatin architecture of the CpG island region from DSC3-negative breast cancer cells lines.RESULTS:DSC3 expression was downregulated in 23 of 32 (72%) breast cancer specimens comprising: 22 invasive ductal carcinomas, 7 invasive lobular breast carcinomas, 2 invasive ductal carcinomas that metastasized to the lymph node, and a mucoid ductal carcinoma. Of the 23 specimens showing a loss of DSC3 expression, 13 (56%) were associated with cytosine hypermethylation of the promoter region. Furthermore, DSC3 expression is limited to cells of epithelial origin and its expression of mRNA and protein is lost in a high proportion of breast tumor cell lines (79%). Lastly, DNA hypermethylation of the DSC3 promoter is highly correlated with a closed chromatin structure.CONCLUSION:These results indicate that the loss of DSC3 expression is a common event in primary breast tumor specimens, and that DSC3 gene silencing in breast tumors is frequently linked to aberrant cytosine methylation and concomitant changes in chromatin structure.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://breast-cancer-research.com/content/7/5/R669en
dc.rights© 2005 Oshiro et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 2.0)en
dc.titleEpigenetic silencing of DSC3 is a common event in human breast canceren
dc.typeArticleen
dc.identifier.eissn1465-542Xen
dc.contributor.departmentDepartments of Pharmacology and Toxicology, Arizona Cancer Center, University of Arizona, Tucson, AZ, USAen
dc.contributor.departmentDepartment of Surgery, Arizona Cancer Center, University of Arizona, Tucson, AZ, USAen
dc.contributor.departmentDepartment of Cell Biology and Anatomy, Arizona Cancer Center, University of Arizona, Tucson, AZ, USAen
dc.contributor.departmentDepartment of Radiation Oncology, Free Radical and Radiation Biology Program, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USAen
dc.identifier.journalBreast Cancer Researchen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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