The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma
| Autor: | Victor R. DeFilippis, J M Carroll, Patrick P. Rose, Klaus Früh, Ashlee V. Moses, M Lagunoff, Charles T. Roberts, P A Carroll |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
medicine.medical_treatment Organophosphonates Naphthalenes Receptor IGF Type 1 Insulin-like growth factor Growth factor receptor Genetics medicine Humans Gammaherpesvirinae RNA Small Interfering Receptor Sarcoma Kaposi Molecular Biology Kaposi's sarcoma Cell Line Transformed biology Growth factor Endothelial Cells virus diseases Cell Transformation Viral medicine.disease biology.organism_classification Receptor Insulin Insulin receptor Herpesvirus 8 Human biology.protein Cancer research Primary effusion lymphoma Mitogen-Activated Protein Kinases |
| Zdroj: | Oncogene. 26:1995-2005 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1210006 |
| Popis: | Kaposi sarcoma (KS), a multifocal neoplasm of the skin that can spread to visceral organs, is the most prevalent malignant tumor in acquired immuno deficiency syndrome (AIDS) patients. KS-associated herpesvirus (KSHV or HHV8) is considered the primary etiological factor of this malignancy, as well as of primary effusion lymphoma and multicentric Castleman's disease. KS lesions are characterized by proliferating spindle cells of endothelial cell (EC) origin. The action of the insulin-like growth factor (IGF) system has been implicated in many malignancies, and recent data have demonstrated that the IGF-I receptor (IGF-IR) is required for in vitro growth of the KS-derived KSIMM cell line. To examine whether the IGF pathway is also involved in KSHV-mediated transformation of ECs, we examined the expression and function of the IGF system in KSHV-infected, immortalized dermal microvascular EC (E-DMVEC). The expression of the insulin receptor (IR) was strongly induced in latently infected E-DMVEC, whereas the expression levels of the IGF-IR remained unchanged. Gene knockdown of IR, but not IGF-IR, prevented the characteristic focus formation seen in KSHV-infected E-DMVEC. Similarly, treatment with the IR-specific small-molecule inhibitor HNMPA-(AM(3)) inhibited postconfluent growth. These data suggest a role for the IR, but not the IGF-IR, in KSHV-induced transformation of vascular ECs. |
| Databáze: | OpenAIRE |
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