K-ras 4A and 4B mRNA levels correlate with superoxide in lung adenocarcinoma cells, while at the protein level, only mutant K-ras 4A protein correlates with superoxide
| Autor: | Lucy M. Anderson, Yih-Horng Shiao, Richard J. Calvert, Meghana Gupta, Anna E. Maciag |
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| Rok vydání: | 2013 |
| Předmět: |
Pulmonary and Respiratory Medicine
Cancer Research Small interfering RNA Lung Neoplasms Carcinogenesis Mutant Adenocarcinoma of Lung Adenocarcinoma Biology medicine.disease_cause Article Proto-Oncogene Proteins p21(ras) chemistry.chemical_compound Superoxides Mutant protein Cell Line Tumor medicine Humans Protein Isoforms RNA Small Interfering Messenger RNA Superoxide Wild type Molecular biology Gene Expression Regulation Neoplastic Oncology chemistry Cell culture Mutation Mutant Proteins |
| Zdroj: | Lung Cancer. 80:263-269 |
| ISSN: | 0169-5002 |
| DOI: | 10.1016/j.lungcan.2013.01.022 |
| Popis: | The K-ras gene is frequently mutated in lung and other cancers. K-ras protein includes two splice variants, K-ras 4A and 4B. While K-ras 4B is more widely expressed, recent evidence implicates K-ras 4A in lung tumorigenesis. We found that K-ras 4A protein has a wide range of expression in a large panel of human lung adenocarcinoma cell lines. In cell lines with mutant K-ras, but not those with wildtype K-ras, the K-ras 4A protein had a strong positive correlation with levels of cellular superoxide. We investigated whether K-ras 4A protein was involved in superoxide production, or alternatively was modulated by elevated superoxide. Experiments with small interfering RNA targeting K-ras 4A did not confirm its role in superoxide generation. However, decreasing cellular superoxide with the scavenger Tiron tended to reduce levels of K-ras 4A protein. K-ras 4A and 4B mRNA were also quantified in a number of NSCLC cell lines. 4A mRNA correlated with 4A protein only in K-ras-mutant cells. K-ras 4A mRNA also correlated with superoxide, but with no difference between cell lines with mutant or wildtype K-ras. K-ras 4B mRNA correlated with 4A mRNA and with superoxide, in both K-ras mutant and wildtype cells. The results are consistent with superoxide directly or indirectly up-regulating expression of all K-ras genes, and also increasing the stability of K-ras 4A mutant protein selectively. |
| Databáze: | OpenAIRE |
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