Abstract 2923: Identification and validation of dysregulated MAPK7 (ERK5) as a novel oncogenic target in squamous cell lung and esophageal carcinoma

MAPK7/ERK5 (extracellular-signal-regulated kinase 5) is the effector kinase of a canonical three-tiered MAPK (mitogen activated protein kinase) signalling cascade comprising MEK (MAPK/ERK kinase) 5, MEKK(MEK kinase) 2/3 and ERK5 itself(1). Under normal physiological conditions, MEK5 and ERK5 are ubiquitously expressed and are activated by growth factors and cellular stresses to perform roles in blood vessel, cardiac and muscle development(2). Although the MAPK7-axis is the least well studied of the MAPK-signaling pathways, evidence suggests that it plays a role in the pathology of cancer, in particular; breast cancer progression, prostate cancer bone metastases and hepatocellular carcinoma(3-5). Array-based comparative genomic hybridisation profiling (aCGH) of non-small cell lung cancer (NSCLC) patient tumor samples initially identified MAPK7 gene amplification as a novel genetic event. To further explore the role of MAPK7 in human cancer, we assessed the true incidence of MAPK7 gene amplification using fluorescence in situ hybridization (FISH) analysis in a cohort of 80 NSCLC and 95 squamous esophageal cancers (sqEC). High level MAPK7 gene amplification was detected in 4% (3/80) of NSCLC (enriched to 6% (3/49) in squamous cell carcinoma) and 2% (2/95) of sqEC. Immunohistochemical (IHC) analysis of the same tissue samples revealed a good correlation of MAPK7 gene amplification and high level protein expression but importantly, also identified a high prevalence of IHC ‘3+’...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Experimental and Molecular Therapeutics Source Type: research