Specific plasmids encoding shRNA molecules directed against growth factor receptors in cell proliferation inhibition and induction phenotype changes relevant to enhancement of anti-tumor immunity. Model of human non-small (NSCLC) and small (SCLC) cell lung cancer lines
P. Kopinski, J. Kowalewski, A. Goc, M. Jankowski, M. Dancewicz, E. Polgesek (Bydgoszcz, Torun, Poland)
Source: Annual Congress 2010 - Pathology of lung cancer
Session: Pathology of lung cancer
Session type: Thematic Poster Session
Number: 3255
Disease area: Thoracic oncology
Abstract BACKGROUND. Activation of IGF-I and EGF family receptors initiate signal transduction in lung cancer cells. Some observation suggest that these oncogenes may participate in immune escape phenomenon. Gene- and immune therapy are considered to be promising treatment options. METHODS: A549 and NCI-H82 cell lines, model of non-small and small cell lung cancer, respectively, were transfected with pLKO.1 plasmids encoding small interfering RNA (siRNA) specific sequences (short hairpin RNA, shRNA) against insuline-like growth factor receptor-1 (IGFR1), epidermic growth factor receptor (EGFR) and HER2/neu. Transfection efficiency was estimated by RT-PCR. Apoptosis (TUNEL assay, cell cycle sub-G1 phase), proliferation as well as expression of B7 costimulatory molecules (CD80, 86), CD83, HLA class I and II, death receptors (Fas, TNFR1, DR3, DR4) and Fas-ligand, were examined before and after transfection. RESULTS (median of 5 experiments, cells transfected with empty vector as control): All oncogene blockade resulted in increased apoptosis rate and repressed proliferation. In both cell lines anti-EGFR and anti-IGFR1 specific transfection caused significantly higher CD86, HLA-I and Fas Ligand expression, but parallel rise in CD80+ cells appeared only in A549 cell line after anti-IGFR1 shRNA (7,5 vs 2,3%, p<0.05). CONCLUSIONS: IGF-I receptor is to be used in some types of non-small cell lung cancer as a molecular target of techniques based on antisense gene therapy, the method promising due to its immunostimulatory potential.
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P. Kopinski, J. Kowalewski, A. Goc, M. Jankowski, M. Dancewicz, E. Polgesek (Bydgoszcz, Torun, Poland). Specific plasmids encoding shRNA molecules directed against growth factor receptors in cell proliferation inhibition and induction phenotype changes relevant to enhancement of anti-tumor immunity. Model of human non-small (NSCLC) and small (SCLC) cell lung cancer lines. Eur Respir J 2010; 36: Suppl. 54, 3255
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