Human Gene Set: MARTIN_VIRAL_GPCR_SIGNALING_DN


Standard name MARTIN_VIRAL_GPCR_SIGNALING_DN
Systematic name M1330
Brief description Down-regulated genes in the expression signature of direct and paracrine viral GPCR signaling in endothelial cells.
Full description or abstract Kaposi's sarcoma (KS) is the most frequent AIDS-associated malignancy, etiologically linked to the infection with the human herpesvirus 8 (HHV-8/KSHV). This member of the gamma-herpesviridae family encodes 81 open reading frames, several bearing oncogenic potential. A constitutively active virally encoded G protein-coupled receptor (vGPCR) readily induces KS-like lesions when expressed in endothelial cells in vivo, and unmasks the oncogenic potential of other HHV-8 genes in a paracrine fashion. How vGPCR causes endothelial cell transformation is still not fully understood. Using full-genome microarray analysis we show here that the expression of nuclear factor-kappaB (NF-kappaB)-regulated genes is a prominent feature triggered by vGPCR in cells expressing this viral oncogene and in cells exposed to vGPCR-induced secretions, thus mimicking its paracrine effect. Indeed, vGPCR activates the NF-kappaB pathway potently, and NF-kappaB activation is a hallmark of both human and experimental KS. Of interest, whereas constitutive NF-kappaB signaling is not sufficient to promote endothelial cells transformation, NF-kappaB function is strictly required for vGPCR-induced direct and paracrine neoplasia. Taken together, these results strongly support the role of NF-kappaB regulated genes in KS pathogenesis, thus providing the rationale for the development of novel mechanism-based therapies for this angioproliferative disease.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17934524   Authors: Martin D,Galisteo R,Ji Y,Montaner S,Gutkind JS
Exact source Table S1B
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Source species Mus musculus
Contributed by Jessica Robertson (Broad Institute)
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identifier namespace		 MOUSE_SEQ_ACCESSION
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Version history 7.0: Renamed from MANTOVANI_VIRAL_GPCR_SIGNALING_DN. Complete metadata update.

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