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dc.contributor.authorPeng, Zhengang
dc.contributor.authorWeber, Jennifer
dc.contributor.authorHan, Zhaosheng
dc.contributor.authorShen, Rulong
dc.contributor.authorZhou, Wenchao
dc.contributor.authorScott, James
dc.contributor.authorChan, Michael, 1963-
dc.contributor.authorLin, Huey-Jen
dc.date.accessioned2016-05-20T09:01:03Z
dc.date.available2016-05-20T09:01:03Z
dc.date.issued2012en
dc.identifier.citationPeng et al. Molecular Cancer 2012, 11:61 http://www.molecular-cancer.com/content/11/1/61en
dc.identifier.doi10.1186/1476-4598-11-61en
dc.identifier.urihttp://hdl.handle.net/10150/610205
dc.description.abstractBACKGROUND:The oncogenic roles contributed by the Akt/PKB kinase family remain controversial and presumably depend on cell context, but are perceived to be modulated by an interplay and net balance between various isoforms. This study is intended to decipher whether distinct Akt kinase isoforms exert either redundant or unique functions in regulating neoplastic features of breast cancer cells, including epithelial-mesenchymal transition (EMT), cell motility, and stem/progenitor cell expansion.RESULTS:We demonstrate that overactivation of Akt signaling in nonmalignant MCF10A cells and in primary cultures of normal human mammary epithelial tissue results in previously unreported inhibitory effects on EMT, cell motility and stem/progenitor cell expansion. Importantly, this effect is largely redundant and independent of Akt isoform types. However, using a series of isogenic cell lines derived from MCF-10A cells but exhibiting varying stages of progressive tumorigenesis, we observe that this inhibition of neoplastic behavior can be reversed in epithelial cells that have advanced to a highly malignant state. In contrast to the tumor suppressive properties of Akt, activated Akt signaling in MCF10A cells can rescue cell viability upon treatment with cytotoxic agents. This feature is regarded as tumor-promoting.CONCLUSION:We demonstrate that Akt signaling conveys novel dichotomy effects in which its oncogenic properties contributes mainly to sustaining cell viability, as opposed to the its tumor suppressing effects, which are mediated by repressing EMT, cell motility, and stem/progenitor cell expansion. While the former exerts a tumor-enhancing effect, the latter merely acts as a safeguard by restraining epithelial cells at the primary sites until metastatic spread can be moved forward, a process that is presumably dictated by the permissive tumor microenvironment or additional oncogenic insults.
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.molecular-cancer.com/content/11/1/61en
dc.rights© 2012 Peng 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.rights.urihttps://creativecommons.org/licenses/by/2.0/
dc.subjectActivated Akt signalingen
dc.subjectBreast epitheliaen
dc.subjectEpithelial-mesenchymal transitionen
dc.subjectMotilityen
dc.subjectStem-progenitor cellsen
dc.titleDichotomy effects of Akt signaling in breast canceren
dc.typeArticleen
dc.identifier.eissn1476-4598en
dc.contributor.departmentDivision of Medical Technology, School of Allied Medical Professions, The Ohio State University, Columbus, OH, 43210, USAen
dc.contributor.departmentMolecular Biology and Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USAen
dc.contributor.departmentDepartment of Pathology, The Ohio State University, Columbus, OH, USAen
dc.contributor.departmentCollege of Medicine, University of Arizona, Phoenix, AZ, USAen
dc.contributor.departmentDepartment of Life Science and Human Epigenomics Center, National Chung Cheng University, Min-Hsiung, Chia-Yi, Taiwan, ROCen
dc.contributor.departmentDepartment of Medical Laboratory Sciences, University of Delaware, Room 305 Willard Hall Education Building, 16 West Main Street, Newark, Delaware, 19716, USAen
dc.identifier.journalMolecular Canceren
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
refterms.dateFOA2018-08-14T21:50:04Z
html.description.abstractBACKGROUND:The oncogenic roles contributed by the Akt/PKB kinase family remain controversial and presumably depend on cell context, but are perceived to be modulated by an interplay and net balance between various isoforms. This study is intended to decipher whether distinct Akt kinase isoforms exert either redundant or unique functions in regulating neoplastic features of breast cancer cells, including epithelial-mesenchymal transition (EMT), cell motility, and stem/progenitor cell expansion.RESULTS:We demonstrate that overactivation of Akt signaling in nonmalignant MCF10A cells and in primary cultures of normal human mammary epithelial tissue results in previously unreported inhibitory effects on EMT, cell motility and stem/progenitor cell expansion. Importantly, this effect is largely redundant and independent of Akt isoform types. However, using a series of isogenic cell lines derived from MCF-10A cells but exhibiting varying stages of progressive tumorigenesis, we observe that this inhibition of neoplastic behavior can be reversed in epithelial cells that have advanced to a highly malignant state. In contrast to the tumor suppressive properties of Akt, activated Akt signaling in MCF10A cells can rescue cell viability upon treatment with cytotoxic agents. This feature is regarded as tumor-promoting.CONCLUSION:We demonstrate that Akt signaling conveys novel dichotomy effects in which its oncogenic properties contributes mainly to sustaining cell viability, as opposed to the its tumor suppressing effects, which are mediated by repressing EMT, cell motility, and stem/progenitor cell expansion. While the former exerts a tumor-enhancing effect, the latter merely acts as a safeguard by restraining epithelial cells at the primary sites until metastatic spread can be moved forward, a process that is presumably dictated by the permissive tumor microenvironment or additional oncogenic insults.


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© 2012 Peng 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).
Except where otherwise noted, this item's license is described as © 2012 Peng 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).