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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3693-3699. Prepublished online as a Blood First Edition Paper on January 12, 2006; DOI 10.1182/blood-2005-04-1505. This Article Full Text (PDF) All Versions of this Article: 2005-04-1505v1 107/9/3693    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kasyapa, C. S Articles by Cowell, J. K Search for Related Content PubMed PubMed Citation Articles by Kasyapa, C. S Articles by Cowell, J. K Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 13, 2005 Accepted December 23, 2005 Induction of the plasminogen activator inhibitor-2 in cells expressing the ZNF198/FGFR1 fusion kinase, that is involved in atypical myeloproliferative disease Chitta S Kasyapa, Padmaja Kunapuli, Lesleyann Hawthorn, and John K Cowell* Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA * Corresponding author; email: john.cowell{at}roswellpark.org. The ZNF198/FGFR1 fusion kinase associated with an atypical myeloproliferative disease is constitutively activated and regulates several STAT transcription factors. We used oligonucleotide microarrays to compare the gene expression profiles between HEK-293 cells that stably express either the ZNF198/FGFR1 chimeric protein or the wild-type ZNF198 gene. Expression of the plasminogen activator inhibitor-2 (PAI-2 /SERPINB2) was highly increased in cells expressing the fusion gene. Western blot analysis demonstrated that HEK-293 cells do not express PAI-2 endogenously, but in ZNF198/FGFR1 expressing cells two molecular forms of PAI-2, which were 47 kd and 32 kd, were expressed intracellularly, and a 60 kd form was secreted. Similarly, expression of ZNF198/FGFR1 in BaF/3 mouse hematopoietic cells also induced the expression of the PAI-2 protein. Immunoprecipitation analysis revealed that both intracellular forms of PAI-2 bind to the ZNF198/FGFR1 kinase. Treatment of HEK-293 and BaF/3 cells with TNFin the presence of cycloheximide, induced apoptosis in both cases. In contrast, HEK-293 and BaF/3 expressing ZNF198/FGFR1 were resistant to TNF-induced apoptosis. These observations suggest that expression of the ZNF198/FGFR1 fusion gene is associated with specific PAI-2 -mediated resistance to apoptosis which may contribute to the highly malignant nature of leukemic cells carrying this fusion kinase gene. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Ren, X. Li, and J. K. Cowell Genetic fingerprinting of the development and progression of T-cell lymphoma in a murine model of atypical myeloproliferative disorder initiated by the ZNF198-fibroblast growth factor receptor-1 chimeric tyrosine kinase Blood, August 20, 2009; 114(8): 1576 - 1584. [Abstract] [Full Text] [PDF] L. Tonnetti, S. Netzel-Arnett, G. A. Darnell, T. Hayes, M. S. Buzza, I. E. Anglin, A. Suhrbier, and T. M. Antalis SerpinB2 Protection of Retinoblastoma Protein from Calpain Enhances Tumor Cell Survival Cancer Res., July 15, 2008; 68(14): 5648 - 5657. [Abstract] [Full Text] [PDF]

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