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dc.contributor.authorPratap, Jitesh
dc.contributor.authorImbalzano, Karen M.
dc.contributor.authorUnderwood, Jean. M.
dc.contributor.authorCohet, Nathalie
dc.contributor.authorGokul, Karthiga Devi
dc.contributor.authorAkech, Jacqueline
dc.contributor.authorVan Wijnen, Andre J.
dc.contributor.authorStein, Janet L.
dc.contributor.authorImbalzano, Anthony N.
dc.contributor.authorNickerson, Jeffrey A.
dc.contributor.authorLian, Jane B.
dc.contributor.authorStein, Gary S.
dc.date2022-08-11T08:09:08.000
dc.date.accessioned2022-08-23T16:18:38Z
dc.date.available2022-08-23T16:18:38Z
dc.date.issued2009-08-20
dc.date.submitted2011-02-08
dc.identifier.citationCancer Res. 2009 Sep 1;69(17):6807-14. Epub 2009 Aug 18. <a href="http://dx.doi.org/10.1158/0008-5472.CAN-09-1471">Link to article on publisher's site</a>
dc.identifier.issn0008-5472 (Linking)
dc.identifier.doi10.1158/0008-5472.CAN-09-1471
dc.identifier.pmid19690135
dc.identifier.urihttp://hdl.handle.net/20.500.14038/34862
dc.description.abstractThe transcription factor Runx2 is highly expressed in breast cancer cells compared with mammary epithelial cells and contributes to metastasis. Here we directly show that Runx2 expression promotes a tumor cell phenotype of mammary acini in three-dimensional culture. Human mammary epithelial cells (MCF-10A) form polarized, growth-arrested, acini-like structures with glandular architecture. The ectopic expression of Runx2 disrupts acini formation, and electron microscopic ultrastructural analysis revealed the absence of lumens. Characterization of the disrupted acini structures showed increased cell proliferation (Ki-67 positive cells), decreased apoptosis (Bcl-2 induction), and loss of basement membrane formation (absence of beta(4) integrin expression). In complementary experiments, inhibition of Runx2 function in metastatic MDA-MB-231 breast cancer cells by stable expression of either short hairpin RNA-Runx2 or a mutant Runx2 deficient in subnuclear targeting resulted in reversion of acini to more normal structures and reduced tumor growth in vivo. These novel findings provide direct mechanistic evidence for the biological activity of Runx2, dependent on its subnuclear localization, in promoting early events of breast cancer progression and suggest a molecular therapeutic target.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=19690135&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1158/0008-5472.CAN-09-1471
dc.subject*Breast Neoplasms
dc.subjectCell Culture Techniques
dc.subjectCell Movement
dc.subjectCell Polarity
dc.subjectCell Proliferation
dc.subject*Cell Transformation, Neoplastic
dc.subjectCells, Cultured
dc.subjectCore Binding Factor Alpha 1 Subunit
dc.subjectEpithelial Cells
dc.subjectFemale
dc.subject*Gene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectImaging, Three-Dimensional
dc.subject*Mammary Glands, Human
dc.subjectMutation
dc.subjectNeoplasm Metastasis
dc.subjectCell Biology
dc.titleEctopic runx2 expression in mammary epithelial cells disrupts formation of normal acini structure: implications for breast cancer progression
dc.typeJournal Article
dc.source.journaltitleCancer research
dc.source.volume69
dc.source.issue17
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/imbalzano/3
dc.identifier.contextkey1771157
html.description.abstract<p>The transcription factor Runx2 is highly expressed in breast cancer cells compared with mammary epithelial cells and contributes to metastasis. Here we directly show that Runx2 expression promotes a tumor cell phenotype of mammary acini in three-dimensional culture. Human mammary epithelial cells (MCF-10A) form polarized, growth-arrested, acini-like structures with glandular architecture. The ectopic expression of Runx2 disrupts acini formation, and electron microscopic ultrastructural analysis revealed the absence of lumens. Characterization of the disrupted acini structures showed increased cell proliferation (Ki-67 positive cells), decreased apoptosis (Bcl-2 induction), and loss of basement membrane formation (absence of beta(4) integrin expression). In complementary experiments, inhibition of Runx2 function in metastatic MDA-MB-231 breast cancer cells by stable expression of either short hairpin RNA-Runx2 or a mutant Runx2 deficient in subnuclear targeting resulted in reversion of acini to more normal structures and reduced tumor growth in vivo. These novel findings provide direct mechanistic evidence for the biological activity of Runx2, dependent on its subnuclear localization, in promoting early events of breast cancer progression and suggest a molecular therapeutic target.</p>
dc.identifier.submissionpathimbalzano/3
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages6807-14


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