Show simple item record

dc.contributor.authorGovindarajan, Baskaran
dc.contributor.authorShah, Asha
dc.contributor.authorCohen, Cynthia
dc.contributor.authorArnold, Rebecca S.
dc.contributor.authorSchechner, Jeffrey
dc.contributor.authorChung, Jun
dc.contributor.authorMercurio, Arthur M.
dc.contributor.authorAlani, Rhoda
dc.contributor.authorRyu, Byungwoo
dc.contributor.authorFan, Chun-Yang
dc.contributor.authorCuezva, Jose M.
dc.contributor.authorMartinez, Marta
dc.contributor.authorArtbiser, Jack L.
dc.date2022-08-11T08:08:02.000
dc.date.accessioned2022-08-23T15:39:51Z
dc.date.available2022-08-23T15:39:51Z
dc.date.issued2005-02-08
dc.date.submitted2010-11-07
dc.identifier.citationJ Biol Chem. 2005 Apr 8;280(14):13936-43. Epub 2005 Feb 4. <a href="http://dx.doi.org/10.1074/jbc.M500411200">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Linking)
dc.identifier.doi10.1074/jbc.M500411200
dc.identifier.pmid15695519
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26267
dc.description.abstractPlatelet-derived growth factors (PDGFs) comprise a family of growth factors strongly implicated in human oncogenesis. A number of human tumors overexpress PDGF family members or have translocations activating PDGF receptors. Whereas the epidemiologic evidence implicating PDGF in human tumors is strong, malignant transformation of human cells by overexpression of PDGF has not been demonstrated. We have previously developed a human cell line by the sequential introduction of large T cells and telomerase, and we have demonstrated that these cells express functionally active PDGF receptor (PDGFR) beta. In order to determine whether growth factor-mediated transformation of human cells could occur, these cells were transduced with a retrovirus encoding PDGF-BB. Constitutive expression of PDGF-BB led to malignant transformation in nude mice. This is the first demonstration of constitutive signaling causing malignant transformation of human cells. Some of the changes that occur because of constitutive growth factor expression can be reversed by the clinically approved tyrosine kinase inhibitor Glivec, whereas other changes are not reversible by tyrosine kinase inhibitors. Our model allows the assessment of epigenetic changes that occur during human carcinogenesis. In addition, these studies provide insight into the clinical failure of tyrosine kinase inhibitors as monotherapy for advanced malignancy.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=15695519&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1074/jbc.M500411200
dc.subject1-Phosphatidylinositol 3-Kinase
dc.subjectAnimals
dc.subjectAntineoplastic Agents
dc.subjectCell Line
dc.subject*Cell Transformation, Neoplastic
dc.subjectCyclin-Dependent Kinase Inhibitor p16
dc.subject*Gene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectInhibitor of Differentiation Protein 1
dc.subjectMAP Kinase Signaling System
dc.subjectMale
dc.subjectMice
dc.subjectMice, Nude
dc.subjectMitogen-Activated Protein Kinases
dc.subjectNeoplasm Transplantation
dc.subjectPiperazines
dc.subjectPlatelet-Derived Growth Factor
dc.subjectProtein Kinase Inhibitors
dc.subjectPyrimidines
dc.subjectReceptor, Platelet-Derived Growth Factor beta
dc.subjectRecombinant Fusion Proteins
dc.subjectRepressor Proteins
dc.subjectTranscription Factors
dc.subjectTranscription, Genetic
dc.subjectVascular Endothelial Growth Factor A
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleMalignant transformation of human cells by constitutive expression of platelet-derived growth factor-BB
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume280
dc.source.issue14
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cancerbiology_pp/181
dc.identifier.contextkey1633407
html.description.abstract<p>Platelet-derived growth factors (PDGFs) comprise a family of growth factors strongly implicated in human oncogenesis. A number of human tumors overexpress PDGF family members or have translocations activating PDGF receptors. Whereas the epidemiologic evidence implicating PDGF in human tumors is strong, malignant transformation of human cells by overexpression of PDGF has not been demonstrated. We have previously developed a human cell line by the sequential introduction of large T cells and telomerase, and we have demonstrated that these cells express functionally active PDGF receptor (PDGFR) beta. In order to determine whether growth factor-mediated transformation of human cells could occur, these cells were transduced with a retrovirus encoding PDGF-BB. Constitutive expression of PDGF-BB led to malignant transformation in nude mice. This is the first demonstration of constitutive signaling causing malignant transformation of human cells. Some of the changes that occur because of constitutive growth factor expression can be reversed by the clinically approved tyrosine kinase inhibitor Glivec, whereas other changes are not reversible by tyrosine kinase inhibitors. Our model allows the assessment of epigenetic changes that occur during human carcinogenesis. In addition, these studies provide insight into the clinical failure of tyrosine kinase inhibitors as monotherapy for advanced malignancy.</p>
dc.identifier.submissionpathcancerbiology_pp/181
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages13936-43


This item appears in the following Collection(s)

Show simple item record