|
Carcinogenesis
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Furthermore, our experimental analyses demonstrate the functional roles of mutant GNAO1 (a Galpha subunit) and mutant MAP2K4 (a member of the JNK signalling pathway) in oncogenesis.
|
20668451 |
2010 |
|
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
MKK4 (mitogen-activated protein kinase kinase 4, NM_003010.2), which belongs to the mitogen-activated protein kinase pathways, possesses functions in tumorigenesis.
|
19610067 |
2009 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Overexpression of these genes was significantly associated to a poor response to treatment (P = .0001 and P = .0049, respectively), tumor progression, and worse overall survival (P = .0052 and P = .0085, respectively), suggesting that MAPK7 and MAP2K4 could play an important role in osteosarcoma tumorigenesis.
|
22154052 |
2012 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
To understand the pathobiologic roles of MKK4 in tumorigenesis, we examined the phenotypic changes in response to perturbation of the MKK4 expression in breast and pancreatic cancer cell lines.
|
15184866 |
2004 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
We sought to investigate whether promoter methylation, loss of heterozygosity, or changes in phosphorylation are involved in MKK4 dysregulation during ovarian carcinogenesis.
|
17276500 |
2007 |
|
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
Taken together, these results suggest that activated Ki-Ras-mediated signals are involved in the SEK1-JNK pathway through a PKC isotype that is distinct from that involved in MEK1/2-ERK activation in human colon cancer cells and independent of phosphoinositol 3-kinase activation, and the imbalance between ERK and JNK activity caused by activated Ki-Ras may play critical roles in human colorectal tumorigenesis.
|
10344756 |
1999 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
To explore the likelihood that MKK4 acts as a suppressor in gastric tumorigenesis, we examined the expression and mutation status of MKK4 in 144 gastric tissues and cell line specimens.
|
12376211 |
2002 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations, and tumorigenesis.
|
22335172 |
2012 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
These findings suggest that MKK4 may function as a suppressor of tumorigenesis or metastasis in certain types of cells.
|
9331070 |
1997 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations and tumorigenesis.
|
20554746 |
2010 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Mitogen-activated protein kinase kinase 4 (MKK4) regulates tumorigenesis as a component of the MKK4 pathway.
|
31157265 |
2019 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Although the null cells resembled the wild-type cells regarding in vitro viability and proliferation in plastic dishes, there was a marked difference in a more relevant in vivo model of experimental metastasis and tumorigenesis.MKK4(-/-) clones injected i.v. produced fewer lung metastases than syngeneic MKK4-competent cells (P = 0.0034).
|
16740690 |
2006 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
MAP2K4 encodes a dual-specificity kinase (mitogen-activated protein kinase kinase 4, or MKK4) that is mutated in a variety of human malignancies, but the biochemical properties of the mutant kinases and their roles in tumorigenesis have not been fully elucidated.
|
21896780 |
2011 |
|
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
MKK4 genetic inactivation has been observed in a subset of pancreatic carcinomas, implicating deregulation of the stress-activated protein kinase pathway in pancreatic carcinogenesis.
|
15623633 |
2004 |
|
Carcinoma
|
0.050 |
GeneticVariation
|
group |
BEFREE |
Given the small size (7%) of the MKK4-negative group (as expected, given the 5%-10% incidence of genetic loss in carcinomas), a Cox proportional hazards analysis was performed, adjusting for age, sex, and tumor stage.
|
17116802 |
2006 |
|
Carcinoma
|
0.050 |
AlteredExpression
|
group |
BEFREE |
Our data indicate that the loss of Mkk4 protein expression in pancreatic carcinomas may be more frequent than suggested by the rates of genetic inactivation alone and that MKK4 loss may contribute to disease progression.
|
15623633 |
2004 |
|
Carcinoma
|
0.050 |
AlteredExpression
|
group |
BEFREE |
Additionally, downregulation of MKK4 expression was found in 96 (75%) of 128 ovarian serous carcinomas as compared to benign ovarian tissues.
|
16627982 |
2006 |
|
Carcinoma
|
0.050 |
GeneticVariation
|
group |
BEFREE |
Double-equivocal carcinomas showed TP53 (6/29, 20%), PIK3CA (3/29, 10%), HER2 (1/29, 3%), and MAP2K4 (1/29, 3%) mutations.
|
29975246 |
2018 |
|
Carcinoma
|
0.050 |
AlteredExpression
|
group |
BEFREE |
Expression of the MKK4 transcript was easily detectable in all normal and benign tumour tissues and none of 102 primary carcinomas and cell lines showed an abnormal reduction in MKK4 expression.
|
12376211 |
2002 |
|
Carcinoma of lung
|
0.040 |
GeneticVariation
|
disease |
BEFREE |
Our data suggest that the functional -1304G variant in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity and that the G variant may be a marker for susceptibility to lung cancer.
|
20554746 |
2010 |
|
Carcinoma of lung
|
0.040 |
Biomarker
|
disease |
BEFREE |
Evidence that phosphatidylinositol 3-kinase- and mitogen-activated protein kinase kinase-4/c-Jun NH2-terminal kinase-dependent Pathways cooperate to maintain lung cancer cell survival.
|
12714585 |
2003 |
|
Carcinoma of lung
|
0.040 |
Biomarker
|
disease |
BEFREE |
Subsequent analysis showed that the TGFβ/TGFβ receptor/PKA/MKK4 and -7/JNK pathway cascade phosphorylates and induces nuclear export of NR4A1, which in turn forms an active complex with Axin2, Arkadia (RNF111), and RNF12 (RLIM) to induce proteasome-dependent degradation of SMAD7 and enhance lung cancer cell migration.
|
30072581 |
2018 |
|
Carcinoma of lung
|
0.040 |
GeneticVariation
|
disease |
BEFREE |
Functional polymorphism MKK4 -1304T>G has been showed to be protective in colorectal cancer or lung cancer.
|
21702039 |
2012 |
|
Carcinoma, Endometrioid
|
0.020 |
AlteredExpression
|
disease |
BEFREE |
High-grade endometrioid adenocarcinoma (G2 and G3) (p = 0.024), postmenopausal status (p = 0.018), and patient age (≥ 60) (p = 0.012) were significantly correlated with lower MKK4 expression.
|
21372598 |
2010 |
|
Carcinoma, Endometrioid
|
0.020 |
Biomarker
|
disease |
BEFREE |
MAP2K4 is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort.
|
21575258 |
2011 |