RGD Reference Report - Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma. - Rat Genome Database

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Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma.

Authors: Oka, H  Chatani, Y  Hoshino, R  Ogawa, O  Kakehi, Y  Terachi, T  Okada, Y  Kawaichi, M  Kohno, M  Yoshida, O 
Citation: Oka H, etal., Cancer Res. 1995 Sep 15;55(18):4182-7.
RGD ID: 2292629
Pubmed: PMID:7664295   (View Abstract at PubMed)

Mitogen-activated protein kinases (MAPKs) play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAPK cascade, which includes MEK (also known as MAP kinase kinase), Raf-1, and Ras. In this study, we examined whether constitutive activation of the MAPK cascade was associated with the carcinogenesis of human renal cell carcinomas in a series of 25 tumors and in corresponding normal kidneys. Constitutive activation of MAPKs in tumor tissue, as determined by the appearance of phosphorylated forms, was found in 12 cases (48%), and this activation was confirmed by a direct in vitro kinase assay of immunoprecipitate using myelin basic protein as the substrate. The phosphorylation of MEK and of Raf-1, as monitored by a mobility shift in SDS-PAGE, which is reportedly associated with the activation of these kinases, occurred in 9 of 18 cases (50%) and in 6 of 11 cases (55%) respectively. The activation of MAPKs was correlated with MEK activation (P = 0.0045) and with Raf-1 activation (P = 0.067). Furthermore, overexpression of MEK was found in 13 of 25 cases (52%) by Western blot analysis, and this overexpression was associated significantly with MAPK activation (P = 0.034). No mutations were noted in H-,K-, or N-ras genes by PCR direct sequencing in any of the 25 tumor samples. Of the patients studied, 8 of 18 (44%) stage pT2 patients and four of six (67%) stage pT3 patients showed MAPK activation. The single stage pT1 patient did not evidence MAPK activation. Furthermore, one of seven (14%) grade 1 patients, 9 of 13 (69%) grade 2 patients, and two of five (40%) grade 3 patients showed MAPK activation (grade 1 versus grades 2 and 3, P = 0.046). Our results suggest that constitutive activation of MAPKs may be associated with the carcinogenesis of human RCCs.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal cell carcinoma  IEP 2292629protein:increased expression:tumor:13/25 cases (52%)RGD 
renal cell carcinoma  ISOMAP2K1 (Homo sapiens)2292629; 2292629 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Map2k1  (mitogen activated protein kinase kinase 1)

Genes (Mus musculus)
Map2k1  (mitogen-activated protein kinase kinase 1)

Genes (Homo sapiens)
MAP2K1  (mitogen-activated protein kinase kinase 1)


Additional Information