Characterization of c-Kit expression and activation in KSHV-infected endothelial cells

Janet Douglas, Jill G. Whitford, Ashlee Moses

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Kaposi's sarcoma (KS) herpesvirus (KSHV) is the etiological agent of several immunodeficiency-linked cancers, including KS. Our previous work showed that the proto-oncogene c-kit is upregulated in KSHV-infected endothelial cells (ECs), as well as in KS lesions. We show here that KSHV-dependent induction of both c-kit mRNA and protein requires the establishment of a latent infection and that this upregulation occurs in primary DMVECs as well as in immortalized DMVECs (eDMVECs). Interestingly, we find that while the lymphatic EC (LEC) subpopulation exhibits KSHV-induced c-Kit upregulation, the blood EC (BEC) subpopulation does not. Despite this upregulation of c-Kit, receptor activation and phosphorylation of downstream effectors such as MAP Kinase Erk 1/2 and GSK-3 still requires the addition of exogenous c-Kit ligand, stem cell factor (SCF). These data indicate that KSHV does not induce constitutive c-Kit signaling, but instead upregulates c-Kit receptor levels, thus allowing infected ECs to respond to endogenous and exogenous SCF. Nonetheless, inhibition of either c-Kit activation or its downstream effectors reverses the characteristic spindle phenotype of infected eDMVECs. Together, these results contribute to our overall understanding of the role that the c-kit proto-oncogene plays in KS pathogenesis.

Original languageEnglish (US)
Pages (from-to)174-185
Number of pages12
JournalVirology
Volume390
Issue number2
DOIs
StatePublished - Aug 1 2009

Fingerprint

Herpesviridae
Kaposi's Sarcoma
Proto-Oncogene Proteins c-kit
Endothelial Cells
Stem Cell Factor
Up-Regulation
Proto-Oncogenes
Glycogen Synthase Kinase 3
Blood Cells
Phosphotransferases
Phosphorylation
Phenotype
Messenger RNA
Infection
Neoplasms

Keywords

  • c-kit
  • Endothelial cells
  • Herpesvirus 8
  • Kaposi's sarcoma
  • KSHV
  • Viral transformation

ASJC Scopus subject areas

  • Virology

Cite this

Characterization of c-Kit expression and activation in KSHV-infected endothelial cells. / Douglas, Janet; Whitford, Jill G.; Moses, Ashlee.

In: Virology, Vol. 390, No. 2, 01.08.2009, p. 174-185.

Research output: Contribution to journalArticle

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