Expression Profiling during Mammary Epithelial Cell Three-Dimensional Morphogenesis Identifies PTPRO as a Novel Regulator of Morphogenesis and ErbB2-Mediated Transformation

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Published inMolecular and Cellular Biology Vol. 32; no. 19; pp. 3913 - 3924
Main Authors Yu, Min, Lin, Guang, Arshadi, Niloofar, Kalatskaya, Irina, Xue, Bin, Haider, Syed, Nguyen, Francis, Boutros, Paul C., Elson, Ari, Muthuswamy, Lakshmi B., Tonks, Nicholas K., Muthuswamy, Senthil K.
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.10.2012
Taylor & Francis
Subjects
Breast - metabolism
Breast - pathology
Breast Neoplasms - diagnosis
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cell Death
Cell Line, Tumor
Cell Proliferation
Down-Regulation
Female
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Humans
Mammary Glands, Human - cytology
Mammary Glands, Human - growth & development
Mammary Glands, Human - metabolism
Prognosis
Protein Structure, Tertiary
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - metabolism
Receptor-Like Protein Tyrosine Phosphatases, Class 3 - chemistry
Receptor-Like Protein Tyrosine Phosphatases, Class 3 - genetics
Receptor-Like Protein Tyrosine Phosphatases, Class 3 - metabolism
Transcriptome
Up-Regulation
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Abstract Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to MCB .asm.org, visit: MCB       
AbstractList Identification of genes that are upregulated during mammary epithelial cell morphogenesis may reveal novel regulators of tumorigenesis. We have demonstrated that gene expression programs in mammary epithelial cells grown in monolayer cultures differ significantly from those in three-dimensional (3D) cultures. We identify a protein tyrosine phosphate, PTPRO, that was upregulated in mature MCF-10A mammary epithelial 3D structures but had low to undetectable levels in monolayer cultures. Downregulation of PTPRO by RNA interference inhibited proliferation arrest during morphogenesis. Low levels of PTPRO expression correlated with reduced survival for breast cancer patients, suggesting a tumor suppressor function. Furthermore, we showed that the receptor tyrosine kinase ErbB2/HER2 is a direct substrate of PTPRO and that loss of PTPRO increased ErbB2-induced cell proliferation and transformation, together with tyrosine phosphorylation of ErbB2. Moreover, in patients with ErbB2-positive breast tumors, low PTPRO expression correlated with poor clinical prognosis compared to ErbB2-positive patients with high levels of PTPRO. Thus, PTPRO is a novel regulator of ErbB2 signaling, a potential tumor suppressor, and a novel prognostic marker for patients with ErbB2-positive breast cancers. We have identified the protein tyrosine phosphatase PTPRO as a regulator of three-dimensional epithelial morphogenesis of mammary epithelial cells and as a regulator of ErbB2-mediated transformation. In addition, we demonstrated that ErbB2 is a direct substrate of PTPRO and that decreased expression of PTPRO predicts poor prognosis for ErbB2-positive breast cancer patients. Thus, our results identify PTPRO as a novel regulator of mammary epithelial transformation, a potential tumor suppressor, and a predictive biomarker for breast cancer.
Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to MCB .asm.org, visit: MCB       
Author Lakshmi B. Muthuswamy
Syed Haider
Min Yu
Paul C. Boutros
Francis Nguyen
Senthil K. Muthuswamy
Bin Xue
Niloofar Arshadi
Nicholas K. Tonks
Irina Kalatskaya
Ari Elson
Guang Lin
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  fullname: Muthuswamy, Senthil K.
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  organization: Ontario Cancer Institute, Campbell Family Institute for Breast Cancer Research, Department of Medical Biophysics, University of Toronto
BackLink https://www.ncbi.nlm.nih.gov/pubmed/22851698$$D View this record in MEDLINE/PubMed
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Snippet Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley...
Identification of genes that are upregulated during mammary epithelial cell morphogenesis may reveal novel regulators of tumorigenesis. We have demonstrated...
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StartPage 3913
SubjectTerms Breast - metabolism
Breast - pathology
Breast Neoplasms - diagnosis
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cell Death
Cell Line, Tumor
Cell Proliferation
Down-Regulation
Female
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Humans
Mammary Glands, Human - cytology
Mammary Glands, Human - growth & development
Mammary Glands, Human - metabolism
Prognosis
Protein Structure, Tertiary
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - metabolism
Receptor-Like Protein Tyrosine Phosphatases, Class 3 - chemistry
Receptor-Like Protein Tyrosine Phosphatases, Class 3 - genetics
Receptor-Like Protein Tyrosine Phosphatases, Class 3 - metabolism
Transcriptome
Up-Regulation
Title Expression Profiling during Mammary Epithelial Cell Three-Dimensional Morphogenesis Identifies PTPRO as a Novel Regulator of Morphogenesis and ErbB2-Mediated Transformation
URI http://mcb.asm.org/content/32/19/3913.abstract
https://www.tandfonline.com/doi/abs/10.1128/MCB.00068-12
https://www.ncbi.nlm.nih.gov/pubmed/22851698
https://search.proquest.com/docview/1039202941
https://pubmed.ncbi.nlm.nih.gov/PMC3457532
Volume 32
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