Gene Set: MANTOVANI_NFKB_TARGETS_DN

Standard name MANTOVANI_NFKB_TARGETS_DN
Systematic name M1326
Brief description NF-kB-controlled genes down-regulated in endothelial cells in response to viral GPCR protein.
Full description or abstract The cAMP-protein kinase A (PKA) pathway is the major signal transduction pathway involved in melanocyte-stimulating hormone receptor-mediated signaling and melanin production, whereas its role in the control of melanocyte proliferation is still controversial. In this study, we evaluated the effects of selective activation of the different PKA regulatory subunits type 1A (R1A) and type 2B (R2B) on melanocyte proliferation. Immunohistochemistry demonstrated that normal melanocytes lacked R1A protein whereas this subunit was highly expressed in all human melanomas studied (N=20) and in six human melanoma cell lines. Pharmacological activation of the R2 subunits by the cAMP analogue 8-Cl-cAMP inhibited proliferation and increased caspase-3 activity by 68.77+/-10.5 and 72+/-9% respectively, in all cell lines with the exception of the only p53-mutated one. Similar effects were obtained by activating R2 subunits with other analogues and by silencing R1A expression. The antiproliferative and proapoptotic effects of 8-Cl-cAMP were comparable to those observed with commonly used antitumoral drugs. Moreover, 8-Cl-cAMP potentiated the effects of these drugs on both cell proliferation and caspase-3 activity. In conclusion, this study first reports that human melanomas are characterized by a high R1/R2 ratio and that pharmacological and genetic manipulations able to revert this unbalanced expression cause significant antiproliferative and proapoptotic effects in melanoma cells.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17906691   Authors: Mantovani G,Bondioni S,Lania AG,Rodolfo M,Peverelli E,Polentarutti N,Veliz Rodriguez T,Ferrero S,Bosari S,Beck-Peccoz P,Spada A
Exact source Table 2b
Related gene sets (show 3 additional gene sets from the source publication)

(show 4 gene sets from the same authors)
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Organism Mus musculus
Contributed by Jessica Robertson (Broad Institute)
Source platform SEQ_ACCESSION
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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