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10:13

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Quantitative cell signalling analysis reveals down-regulation of MAPK pathway activation in colorectal cancer

Christian Gulmann1, Katherine M Sheehan, Ronán M Conroy

  • 1Department of Pathology, Beaumont Hospital, Dublin, Ireland. christiangulmann@beaumont.ie

The Journal of Pathology
|April 28, 2009
PubMed

Insights

Mitogen-activated protein kinases (MAPK) activity appears down-regulated in colorectal cancer. Activated MAPK isoforms like p-ERK and p-p38 were decreased in tumors compared to normal tissue, suggesting caution for kinase inhibitor therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitogen-activated protein kinases (MAPK) are implicated in colorectal cancer development.
  • Kinase inhibitor therapy is a potential treatment strategy for this disease.
  • Phospho-specific antibodies enable direct measurement of phosphorylated protein isoforms.

Purpose of the Study:

  • To investigate the levels of activated MAPK signaling pathways in colorectal cancer tissues.
  • To compare MAPK activity in cancerous versus normal colorectal mucosa.
  • To evaluate the potential implications for kinase inhibitor therapy.

Main Methods:

  • Laser capture microdissection of epithelium and stroma from 35 colorectal cancer samples and normal mucosa.
  • Reverse-phase protein microarray analysis using phospho-specific antibodies against MAPK pathway components (ERK, p38, JNK, MEK).
  • Western blotting validation of microarray findings.

Main Results:

  • Total MAPK protein levels were unchanged or slightly elevated in cancers.
  • Activated MAPK isoforms (p-ERK, p-p38, p-JNK) were significantly decreased (two- to four-fold) in cancers compared to normal mucosa.
  • Lower expression of p-ERK and p-p38 was observed in advanced Dukes' stages (B and C) compared to stage A, though not statistically significant.

Conclusions:

  • MAPK signaling activity may be down-regulated in colorectal cancer.
  • The findings suggest that kinase inhibitor therapy for colorectal cancer warrants careful evaluation.
  • Further studies in larger cohorts are needed to confirm these results.

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