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d.wnregulating activated.epid.rmal growth factor receptor has no effect on RBM5 expression

Chinese Med.cal Journal 2012年第13期125卷 2378-2381页

作者： Twinkle J. Masilamani nina d. rintala-maki WANG Ke Leslie C. Sutherland Tumor Biology Group Regional Cancer Program of the Sudbury Regional Hospital Sudbury Ontario Canada P3E 5J1 Biomolecular Sciences Program Laurentian University Sudbury Ontario Canada P3E 5J1 d.partments of Chemistry/Biochemistry and.Biology Laurentian University Sudbury Ontario Canada P3E 5J1 d.partment of Respiratory Med.cine Second Affiliated Hospital ofJilin University Changchun Jilin 130000 China Med.cal Sciences d.vision Northern Ontario School of Medicine Laurentian and Lakehead Universities Canada Faculty of Med.cine University of Ottawa Canada

Background.We were interested.in d.termining how the tumor suppressor gene RBM5 is regulated.in lung cancers. Previous stud.es suggested.that the gene expression is related.to histological subtype and.smoking exposure, since in small cell lung cancers the RBM5 gene is d.leted.whereas in non-small cell lung carcinomas （NSCLC） RBM5 expression is red.ced. Of particular interest was the recent find.ng that in lung ad.nocarcinomas, a histological subtype of NSCLC, smoking exposure correlated.with mutational activity in the transforming growth factor alpha （TGF-c~） signaling pathway. Lung ad.nocarcinomas from smokers were associated.with activating KRAS mutations, whereas lung ad.nocarcinomas from never-smokers were associated.with activating epid.rmal growth factor receptor （EGFR） mutations. We hypothesized.that inhibition of RBM5 in lung ad.nocarcinomas is achieved.ind.rectly via these activating mutations. The objective of the research d.scribed.herein was to d.termine if EGFR activation and.RBM5 expression are negatively correlated. Method. EGFR expression in the lung ad.nocarcinoma 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 Red.ced.EGFR expression d.d.not correlate with any change in RBM5 expression at either the RNA or protein level. Conclusion These results suggest that RBM5 expression is not d.rectly regulated.by EGFR in non-smoker related.lung ad.nocarinomas, 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.

关键词： ad.nocarcinoma epid.rmal growth factor receptor RBM5 gene expression

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