RGD Reference Report - Comparison of liver oncogenic potential among human RAS isoforms. - Rat Genome Database

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Comparison of liver oncogenic potential among human RAS isoforms.

Authors: Chung, Sook In  Moon, Hyuk  Ju, Hye-Lim  Kim, Dae Yeong  Cho, Kyung Joo  Ribback, Silvia  Dombrowski, Frank  Calvisi, Diego F  Ro, Simon Weonsang 
Citation: Chung SI, etal., Oncotarget. 2016 Feb 9;7(6):7354-66. doi: 10.18632/oncotarget.6931.
RGD ID: 14696774
Pubmed: PMID:26799184   (View Abstract at PubMed)
PMCID: PMC4872791   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.6931   (Journal Full-text)

Mutation in one of three RAS genes (i.e., HRAS, KRAS, and NRAS) leading to constitutive activation of RAS signaling pathways is considered a key oncogenic event in human carcinogenesis. Whether activated RAS isoforms possess different oncogenic potentials remains an unresolved question. Here, we compared oncogenic properties among RAS isoforms using liver-specific transgenesis in mice. Hydrodynamic transfection was performed using transposons expressing short hairpin RNA downregulating p53 and an activated RAS isoform, and livers were harvested at 23 days after gene delivery. No differences were found in the hepatocarcinogenic potential among RAS isoforms, as determined by both gross examination of livers and liver weight per body weight ratio (LW/BW) of mice expressing HRASQ61L, KRAS4BG12V and NRASQ61K. However, the tumorigenic potential differed significantly between KRAS splicing variants. The LW/BW ratio in KRAS4AG12V mice was significantly lower than in KRAS4BG12V mice (p < 0.001), and KRAS4AG12V mice lived significantly longer than KRRAS4BG12V mice (p < 0.0001). Notably, tumors from KRAS4AG12V mice displayed higher expression of the p16INK4A tumor suppressor when compared with KRAS4BG12V tumors. Forced overexpression of p16INK4A significantly reduced tumor growth in KRAS4BG12V mice, suggesting that upregulation of p16INK4A by KRAS4AG12V presumably delays tumor development driven by the latter oncogene.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NRASHumanLiver Metastasis  IAGP human gene in a mouse model more ...RGD 
NrasRatLiver Metastasis  ISONRAS (Homo sapiens)human gene in a mouse model more ...RGD 
NrasMouseLiver Metastasis  ISONRAS (Homo sapiens)human gene in a mouse model more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nras  (NRAS proto-oncogene, GTPase)

Genes (Mus musculus)
Nras  (neuroblastoma ras oncogene)

Genes (Homo sapiens)
NRAS  (NRAS proto-oncogene, GTPase)


Additional Information