The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma

P. P. Rose, J. M. Carroll, P. A. Carroll, Victor De Filippis, M. Lagunoff, Ashlee Moses, Charles Roberts, Klaus Frueh

Research output: Contribution to journalArticle

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Abstract

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-(AM3) inhibited postconfluent growth. These data suggest a role for the IR, but not the IGF-IR, in KSHV-induced transformation of vascular ECs.

Original languageEnglish (US)
Pages (from-to)1995-2005
Number of pages11
JournalOncogene
Volume26
Issue number14
DOIs
StatePublished - Mar 29 2007

Fingerprint

Kaposi's Sarcoma
Insulin Receptor
Human Herpesvirus 8
Carcinogenesis
Viruses
Somatomedin Receptors
Somatomedins
Endothelial Cells
Primary Effusion Lymphoma
Gene Knockdown Techniques
Neoplasms
IGF Type 1 Receptor
Skin Neoplasms
Growth
Blood Vessels
Acquired Immunodeficiency Syndrome
Cell Line
Skin

Keywords

  • Endothelial cell
  • Insulin
  • Insulin-like growth factor
  • Kaposi's sarcoma
  • Tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Rose, P. P., Carroll, J. M., Carroll, P. A., De Filippis, V., Lagunoff, M., Moses, A., ... Frueh, K. (2007). The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma. Oncogene, 26(14), 1995-2005. https://doi.org/10.1038/sj.onc.1210006

The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma. / Rose, P. P.; Carroll, J. M.; Carroll, P. A.; De Filippis, Victor; Lagunoff, M.; Moses, Ashlee; Roberts, Charles; Frueh, Klaus.

In: Oncogene, Vol. 26, No. 14, 29.03.2007, p. 1995-2005.

Research output: Contribution to journalArticle

Rose PP, Carroll JM, Carroll PA, De Filippis V, Lagunoff M, Moses A et al. The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma. Oncogene. 2007 Mar 29;26(14):1995-2005. https://doi.org/10.1038/sj.onc.1210006
Rose, P. P. ; Carroll, J. M. ; Carroll, P. A. ; De Filippis, Victor ; Lagunoff, M. ; Moses, Ashlee ; Roberts, Charles ; Frueh, Klaus. / The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's sarcoma. In: Oncogene. 2007 ; Vol. 26, No. 14. pp. 1995-2005.
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