Malignant transformation of human cells by constitutive expression of platelet-derived growth factor-BB
Authors
Govindarajan, BaskaranShah, Asha
Cohen, Cynthia
Arnold, Rebecca S.
Schechner, Jeffrey
Chung, Jun
Mercurio, Arthur M.
Alani, Rhoda
Ryu, Byungwoo
Fan, Chun-Yang
Cuezva, Jose M.
Martinez, Marta
Artbiser, Jack L.
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2005-02-08Keywords
1-Phosphatidylinositol 3-KinaseAnimals
Antineoplastic Agents
Cell Line
*Cell Transformation, Neoplastic
Cyclin-Dependent Kinase Inhibitor p16
*Gene Expression Regulation, Neoplastic
Humans
Inhibitor of Differentiation Protein 1
MAP Kinase Signaling System
Male
Mice
Mice, Nude
Mitogen-Activated Protein Kinases
Neoplasm Transplantation
Piperazines
Platelet-Derived Growth Factor
Protein Kinase Inhibitors
Pyrimidines
Receptor, Platelet-Derived Growth Factor beta
Recombinant Fusion Proteins
Repressor Proteins
Transcription Factors
Transcription, Genetic
Vascular Endothelial Growth Factor A
Cancer Biology
Neoplasms
Metadata
Show full item recordAbstract
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.Source
J Biol Chem. 2005 Apr 8;280(14):13936-43. Epub 2005 Feb 4. Link to article on publisher's siteDOI
10.1074/jbc.M500411200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26267PubMed ID
15695519Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M500411200
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