The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer

Breast cancer is a major cause of cancer-related deaths in American women; therefore, the identification of novel breast-cancer related molecules for the discovery of new markers and drug targets remains essential. The human DEK gene, which encodes a chromatin-binding protein and DNA topology regula...

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Main Authors:	Privette Vinnedge, Lisa M., McClaine, Rebecca, Wagh, Purnima K., Wikenheiser-Brokamp, Kathryn A., Waltz, Susan E., Wells, Susanne I.
Format:	Online
Language:	English
Published:	2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117026/

id	pubmed-3117026
recordtype	oai_dc
spelling	pubmed-31170262011-12-16 The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer Privette Vinnedge, Lisa M. McClaine, Rebecca Wagh, Purnima K. Wikenheiser-Brokamp, Kathryn A. Waltz, Susan E. Wells, Susanne I. Article Breast cancer is a major cause of cancer-related deaths in American women; therefore, the identification of novel breast-cancer related molecules for the discovery of new markers and drug targets remains essential. The human DEK gene, which encodes a chromatin-binding protein and DNA topology regulator, is up-regulated in many types of cancer. DEK has been implicated as an oncogene in breast cancer based on mRNA expression studies, but its functional significance in breast cancer growth and progression has not yet been tested directly. We demonstrate that DEK is highly expressed in breast cancer cells compared to normal tissue, and functionally important for cellular growth, invasion and mammosphere formation. DEK over-expression in non-tumorigenic MCF10A cells resulted in increased growth and motility with a concomitant down-regulation of E-cadherin. Conversely, DEK knockdown in MCF7 and MDA-MB-468 breast cancer cells resulted in decreased growth and motility with up-regulation of E-cadherin. The use of DEK-proficient and -deficient breast cancer cells in orthotopic xenografts provided further in vivo evidence that DEK contributes to tumor growth. Activation of the β-catenin signaling pathway is important for normal and cancer stem cell character, growth and metastasis. We show that DEK expression stimulated and DEK knockdown repressed β-catenin nuclear translocation and activity. Importantly, the expression of constitutively active β-catenin rescued breast cancer invasion defects of DEK knockdown cells. Together, our data indicate that DEK expression stimulates the growth, stem cell character, and motility of breast cancer cells, and that DEK-dependent cellular invasion occurs at least in part via β-catenin activation. 2011-02-14 2011-06-16 /pmc/articles/PMC3117026/ /pubmed/21317931 http://dx.doi.org/10.1038/onc.2011.2 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Privette Vinnedge, Lisa M. McClaine, Rebecca Wagh, Purnima K. Wikenheiser-Brokamp, Kathryn A. Waltz, Susan E. Wells, Susanne I.
spellingShingle	Privette Vinnedge, Lisa M. McClaine, Rebecca Wagh, Purnima K. Wikenheiser-Brokamp, Kathryn A. Waltz, Susan E. Wells, Susanne I. The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer
author_facet	Privette Vinnedge, Lisa M. McClaine, Rebecca Wagh, Purnima K. Wikenheiser-Brokamp, Kathryn A. Waltz, Susan E. Wells, Susanne I.
author_sort	Privette Vinnedge, Lisa M.
title	The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer
title_short	The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer
title_full	The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer
title_fullStr	The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer
title_full_unstemmed	The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer
title_sort	human dek oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer
description	Breast cancer is a major cause of cancer-related deaths in American women; therefore, the identification of novel breast-cancer related molecules for the discovery of new markers and drug targets remains essential. The human DEK gene, which encodes a chromatin-binding protein and DNA topology regulator, is up-regulated in many types of cancer. DEK has been implicated as an oncogene in breast cancer based on mRNA expression studies, but its functional significance in breast cancer growth and progression has not yet been tested directly. We demonstrate that DEK is highly expressed in breast cancer cells compared to normal tissue, and functionally important for cellular growth, invasion and mammosphere formation. DEK over-expression in non-tumorigenic MCF10A cells resulted in increased growth and motility with a concomitant down-regulation of E-cadherin. Conversely, DEK knockdown in MCF7 and MDA-MB-468 breast cancer cells resulted in decreased growth and motility with up-regulation of E-cadherin. The use of DEK-proficient and -deficient breast cancer cells in orthotopic xenografts provided further in vivo evidence that DEK contributes to tumor growth. Activation of the β-catenin signaling pathway is important for normal and cancer stem cell character, growth and metastasis. We show that DEK expression stimulated and DEK knockdown repressed β-catenin nuclear translocation and activity. Importantly, the expression of constitutively active β-catenin rescued breast cancer invasion defects of DEK knockdown cells. Together, our data indicate that DEK expression stimulates the growth, stem cell character, and motility of breast cancer cells, and that DEK-dependent cellular invasion occurs at least in part via β-catenin activation.
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117026/
_version_	1611460361735634944

The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer

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