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Downregulation of mitogen-activated protein kinases in human colon cancers
Background:
Activation of the mitogen-activated protein kinases (MAPKs) appears to play an important role in both proliferation and transformation of various cells; the role of MAPK activation in colorectal cancers has not been clearly defined. The purpose of our study was to determine whether MAPK activity and protein levels were increased in colorectal cancers.
Methods:
Colorectal cancers and adjacent normal mucosa from 21 patients were extracted for protein. Expression levels and activity of the MAPKs (ERK1/2, JNK1, p38 and ERK3) were assessed by immunoblot analysis and in vitro kinase assays, respectively. In addition, changes in myelin basic protein (MBP) kinase activity and autophosphorylation were determined by in-gel kinase assays.
Results:
The activities of ERK1/2, JNK1 and p38 were downregulated in the majority of cancers; ERK3 kinase activity was increased in 10 of 21 cancers. The presence of proteins displaying increased MBP phosphorylation and autophosphorylation was identified specifically in the cancers by in-gel kinase assays.
Conclusions:
Our findings demonstrate that the constitutive activation of ERK1/2, JNK1 and p38 is not a feature of colorectal cancers. Moreover, our in-gel kinase results suggest that protein kinases, other than the MAPKs assessed, may play a more crucial role in colon carcinogenesis.
Insights
Mitogen-activated protein kinases (MAPKs) are not consistently activated in colorectal cancers. Other protein kinases, not assessed here, may drive colon carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Mitogen-activated protein kinases (MAPKs) are implicated in cell proliferation and transformation.
- The specific role of MAPK activation in colorectal cancer (CRC) remains unclear.
Purpose of the Study:
- To investigate MAPK activity and protein levels in colorectal cancers.
- To determine if specific MAPKs (ERK1/2, JNK1, p38, ERK3) are upregulated in CRC.
Main Methods:
- Proteins were extracted from colorectal cancers and adjacent normal mucosa of 21 patients.
- MAPK expression and activity were assessed using immunoblot analysis and in vitro kinase assays.
- Myelin basic protein (MBP) kinase activity and autophosphorylation were evaluated via in-gel kinase assays.
Main Results:
- Activities of ERK1/2, JNK1, and p38 were downregulated in most CRC samples.
- ERK3 kinase activity was elevated in 10 out of 21 CRC cases.
- In-gel kinase assays revealed increased MBP phosphorylation and autophosphorylation specifically in cancer tissues.
Conclusions:
- Constitutive activation of ERK1/2, JNK1, and p38 is not characteristic of colorectal cancers.
- Results suggest that protein kinases beyond the studied MAPKs are likely more critical in colon carcinogenesis.