title: Downregulating activated epidermal growth factor receptor has no effect on RBM5 expression.
abstract: BACKGROUND
  We were interested in determining how the tumor suppressor gene RBM5 is regulated in lung cancers. Previous studies suggested that the gene expression is related to histological subtype and smoking exposure, since in small cell lung cancers the RBM5 gene is deleted whereas in non-small cell lung carcinomas (NSCLC) RBM5 expression is reduced. Of particular interest was the recent finding that in lung adenocarcinomas, a histological subtype of NSCLC, smoking exposure correlated with mutational activity in the transforming growth factor alpha (TGF-a) signaling pathway. Lung adenocarcinomas from smokers were associated with activating KRAS mutations, whereas lung adenocarcinomas from never-smokers were associated with activating epidermal growth factor receptor (EGFR) mutations. We hypothesized that inhibition of RBM5 in lung adenocarcinomas is achieved indirectly via these activating mutations. The objective of the research described herein was to determine if EGFR activation and RBM5 expression are negatively correlated.
  
  
  METHODS
  EGFR expression in the lung adenocarcinoma cell line NCI-H1975 was inhibited using small interfering RNA. RBM5 expression was examined by real-time quantitative polymerase chain reaction and Western blotting.
  
  
  RESULTS
  Reduced EGFR expression did not correlate with any change in RBM5 expression at either the RNA or protein level.
  
  
  CONCLUSIONS
  These results suggest that RBM5 expression is not directly regulated by EGFR in non-smoker related lung adenocarinomas, and that some other mechanism operates to inhibit either the expression or function of this potential tumour suppressor in lung cancers that retain the RBM5 gene.
authors.affiliation: Tumor Biology Group, Regional Cancer Program of the Sudbury Regional Hospital, Sudbury, Ontario, Canada P3E 5J1.
authors.forename: Twinkle J
authors.initials: TJ
authors.lastname: Masilamani
authors.forename: Nina D
authors.initials: ND
authors.lastname: Rintala-Maki
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Sutherland
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C473448:RBM5 protein, human; D016601:RNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D066246:ErbB Receptors