Mitogen‐activated protein kinase expression and activation does not differentiate benign from malignant mesothelial cells
- 13 April 2005
- Vol. 103 (11), 2427-2433
- https://doi.org/10.1002/cncr.21014
Abstract
BACKGROUND In vitro studies of malignant mesothelioma (MM) cells have suggested activation of mitogen‐activated protein kinase (MAPK) in response to asbestos exposure. The objective of this study was to investigate protein expression (level) and phosphorylation status (activity) of the extracellular‐regulated kinase (ERK), the c‐Jun amino‐terminal kinase (JNK), and the high‐osmolarity glycerol response kinase (p38) in vivo through the analysis of fresh frozen reactive mesothelium (RM) and MM specimens. METHODS MAPK levels were analyzed in 36 fresh‐frozen MM specimens (32 effusions, 4 biopsies) and in 14 RM specimens (all effusions) using immunoblotting with antibodies detecting the total (pan‐) and activated (phospho‐) fraction (p‐) of ERK, JNK, and p38. Values for pan‐MAPK and p‐MAPK expression and the p‐MAPK/pan‐MAPK ratio in MM and RM specimens were compared. Results were corroborated using immunocytochemistry for p‐ERK, p‐JNK, and p‐38 in selected specimens. RESULTS Pan‐ERK, pan‐JNK, and pan‐p38 expression was found frequently in both MM specimens (35 of 36 specimens) and RM specimens (14 of 14 specimens) using immunoblotting, with comparable findings for activated p‐p38 (34 of 36 MM specimens, 13 of 14 RM specimens). Activation of p‐ERK (27 of 36 MM specimens, 10 of 14 RM specimens) and p‐JNK (25 of 36 MM specimens, 10 of 14 RM specimens) was less frequent. Pan‐ERK (P = 0.016), pan‐JNK (P = 0.004), pan‐p38 (P = 0.012), and p‐ERK (P = 0.02) expression levels were higher in MM specimens from female patients. Pan‐p38 expression levels also were higher in peritoneal MM specimens (P = 0.019). MM and RM showed similar MAPK expression, activation, and activation ratios (Mann–Whitney test; P > 0.05). Immunocytochemistry localized MAPK to MM and RM cells. CONCLUSIONS The current results provided the first evidence of in vivo activation of MAPK in clinical MM and RM. The similar values in these two cell types suggest that MAPK may not be involved in the transformation of benign to malignant mesothelium, thus bringing into question the validity of using MAPKs as molecular therapeutic targets in patients with MM. Cancer 2005. © 2005 American Cancer Society.Keywords
This publication has 27 references indexed in Scilit:
- Activation of p38 MAP kinase by asbestos in rat mesothelial cells is mediated by oxidative stressAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2004
- The Role of Desmin and N-Cadherin in Effusion CytologyThe American Journal of Surgical Pathology, 2001
- The Hallmarks of CancerCell, 2000
- Redox-Mediated Gene Therapies for Environmental Injury: Approaches and ConceptsAntioxidants and Redox Signaling, 1999
- Inhibition of Epidermal Growth Factor-Mediated ERK1/2 Activation byin SituElectroporation of Nonpermeant [(alkylamino)methyl]Acrylophenone DerivativesDNA and Cell Biology, 1998
- v-Ras and v-Raf Block Differentiation of Transformable C3H10T1/2-Derived Preadipocytes at Lower Levels Than Required for Neoplastic TransformationExperimental Cell Research, 1997
- Acute hypertension activates mitogen-activated protein kinases in arterial wall.JCI Insight, 1996
- Opposing Effects of ERK and JNK-p38 MAP Kinases on ApoptosisScience, 1995
- MAPKs: new JNK expands the groupTrends in Biochemical Sciences, 1994
- Survival patterns for malignant mesothelioma: The seer experienceInternational Journal of Cancer, 1988