This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moses, A. V.
Right arrow Articles by Früh, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moses, A. V.
Right arrow Articles by Früh, K.

 Previous Article  |  Next Article 

Journal of Virology, August 2002, p. 8383-8399, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8383-8399.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Kaposi's Sarcoma-Associated Herpesvirus-Induced Upregulation of the c-kit Proto-Oncogene, as Identified by Gene Expression Profiling, Is Essential for the Transformation of Endothelial Cells

Ashlee V. Moses,1* Michael A. Jarvis,1 Camilo Raggo,1 Yolanda C. Bell,3 Rebecca Ruhl,1 B. G. Mattias Luukkonen,3 Diana J. Griffith,4 Cecily L. Wait,4 Brian J. Druker,4 Michael C. Heinrich,4 Jay A. Nelson,1,2 and Klaus Früh1*

Vaccine and Gene Therapy Institute,1 Department of Molecular Microbiology and Immunology, Oregon Health and Science University,2 Division of Hematology and Medical Oncology, Oregon Health and Science University and Portland Veterans Affairs Medical Center, Portland, Oregon 97201,4 R. W. Johnson Pharmaceutical Research Institute, San Diego, California 921213

Received 10 April 2002/ Accepted 3 May 2002

Kaposi's sarcoma (KS), the most frequent malignancy afflicting AIDS patients, is characterized by spindle cell formation and vascularization. Infection with KS-associated herpesvirus (KSHV) is consistently observed in all forms of KS. Spindle cell formation can be replicated in vitro by infection of dermal microvascular endothelial cells (DMVEC) with KSHV. To study the molecular mechanism of this transformation, we compared RNA expression profiles of KSHV-infected and mock-infected DMVEC. Induction of several proto-oncogenes was observed, particularly the receptor tyrosine kinase c-kit. Consistent with increased c-Kit expression, KHSV-infected DMVEC displayed enhanced proliferation in response to the c-Kit ligand, stem cell factor (SCF). Inhibition of c-Kit activity with either a pharmacological inhibitor of c-Kit (STI 571) or a dominant-negative c-Kit protein reversed SCF-dependent proliferation. Importantly, inhibition of c-Kit signal transduction reversed the KSHV-induced morphological transformation of DMVEC. Furthermore, overexpression studies showed that c-Kit was sufficient to induce spindle cell formation. Together, these data demonstrate an essential role for c-Kit in KS tumorigenesis and reveal a target for pharmacological intervention.

* Corresponding author. Mailing address: 505 NW 185th Ave., Beaverton, OR 97006. Phone: (503) 418-2735. Fax: (503) 418-2701. E-mail for Klaus Früh: fruehk{at}ohsu.edu. E-mail for Ashlee V. Moses: mosesa{at}ohsu.edu.

Journal of Virology, August 2002, p. 8383-8399, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8383-8399.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • O'Hara, A. J., Wang, L., Dezube, B. J., Harrington, W. J. Jr, Damania, B., Dittmer, D. P. (2009). Tumor suppressor microRNAs are underrepresented in primary effusion lymphoma and Kaposi sarcoma. Blood 113: 5938-5941 [Abstract] [Full Text]  
  • Punj, V., Matta, H., Schamus, S., Yang, T., Chang, Y., Chaudhary, P. M. (2009). Induction of CCL20 production by Kaposi sarcoma-associated herpesvirus: role of viral FLICE inhibitory protein K13-induced NF-{kappa}B activation. Blood 113: 5660-5668 [Abstract] [Full Text]  
  • Maussang, D., Langemeijer, E., Fitzsimons, C. P., Stigter-van Walsum, M., Dijkman, R., Borg, M. K., Slinger, E., Schreiber, A., Michel, D., Tensen, C. P., van Dongen, G. A.M.S., Leurs, R., Smit, M. J. (2009). The Human Cytomegalovirus-Encoded Chemokine Receptor US28 Promotes Angiogenesis and Tumor Formation via Cyclooxygenase-2. Cancer Res. 69: 2861-2869 [Abstract] [Full Text]  
  • Bull, T. M., Meadows, C. A., Coldren, C. D., Moore, M., Sotto-Santiago, S. M., Nana-Sinkam, S. P., Campbell, T. B., Geraci, M. W. (2008). Human Herpesvirus-8 Infection of Primary Pulmonary Microvascular Endothelial Cells. Am. J. Respir. Cell Mol. Bio. 39: 706-716 [Abstract] [Full Text]  
  • Rose, P. P., Bogyo, M., Moses, A. V., Fruh, K. (2007). Insulin-Like Growth Factor II Receptor-Mediated Intracellular Retention of Cathepsin B Is Essential for Transformation of Endothelial Cells by Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 81: 8050-8062 [Abstract] [Full Text]  
  • Sengupta, S., den Boon, J. A., Chen, I-H., Newton, M. A., Dahl, D. B., Chen, M., Cheng, Y.-J., Westra, W. H., Chen, C.-J., Hildesheim, A., Sugden, B., Ahlquist, P. (2006). Genome-Wide Expression Profiling Reveals EBV-Associated Inhibition of MHC Class I Expression in Nasopharyngeal Carcinoma. Cancer Res. 66: 7999-8006 [Abstract] [Full Text]  
  • Raggo, C., Ruhl, R., McAllister, S., Koon, H., Dezube, B. J., Fruh, K., Moses, A. V. (2005). Novel Cellular Genes Essential for Transformation of Endothelial Cells by Kaposi's Sarcoma-Associated Herpesvirus. Cancer Res. 65: 5084-5095 [Abstract] [Full Text]  
  • Cheung, M. C., Pantanowitz, L., Dezube, B. J. (2005). AIDS-Related Malignancies: Emerging Challenges in the Era of Highly Active Antiretroviral Therapy. The Oncologist 10: 412-426 [Abstract] [Full Text]  
  • Koon, H. B., Bubley, G. J., Pantanowitz, L., Masiello, D., Smith, B., Crosby, K., Proper, J., Weeden, W., Miller, T. E., Chatis, P., Egorin, M. J., Tahan, S. R., Dezube, B. J. (2005). Imatinib-Induced Regression of AIDS-Related Kaposi's Sarcoma. JCO 23: 982-989 [Abstract] [Full Text]  
  • Masood, R., Xia, G., Smith, D. L., Scalia, P., Still, J. G., Tulpule, A., Gill, P. S. (2005). Ephrin B2 expression in Kaposi sarcoma is induced by human herpesvirus type 8: phenotype switch from venous to arterial endothelium. Blood 105: 1310-1318 [Abstract] [Full Text]  
  • McAllister, S. C., Hansen, S. G., Ruhl, R. A., Raggo, C. M., DeFilippis, V. R., Greenspan, D., Fruh, K., Moses, A. V. (2004). Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells. Blood 103: 3465-3473 [Abstract] [Full Text]  
  • Naranatt, P. P., Krishnan, H. H., Svojanovsky, S. R., Bloomer, C., Mathur, S., Chandran, B. (2004). Host Gene Induction and Transcriptional Reprogramming in Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8)-Infected Endothelial, Fibroblast, and B Cells: Insights into Modulation Events Early during Infection. Cancer Res. 64: 72-84 [Abstract] [Full Text]  
  • Dourmishev, L. A., Dourmishev, A. L., Palmeri, D., Schwartz, R. A., Lukac, D. M. (2003). Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis. Microbiol. Mol. Biol. Rev. 67: 175-212 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»