Attenuation of catalase activity in the malignant phenotype plays a functional role in an in vitro model for tumor progression

• Published in: Cancer letters Vol. 173; no. 2; pp. 115 - 125
• Main Authors: Gupta, Ashok, Butts, Brent, Kwei, Kevin A., Dvorakova, Katerina, Stratton, Steven P., Briehl, Margaret M., Bowden, G.Tim
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 28.11.2001; Elsevier
• Subjects: Animals; Antioxidants - metabolism; Biological and medical sciences; Blotting, Northern; Blotting, Western; Catalase; Catalase - metabolism; Catalase - physiology; Cell Line; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Disease Progression; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Glutathione - metabolism; Keratinocytes - metabolism; Methylnitronitrosoguanidine; Mice; Mice, Nude; Molecular and cellular biology; Mutation; Neoplasm Metastasis; Oxygen - metabolism; Phenotype; Plasmids - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; RNA, Messenger - metabolism; Skin cancer; Superoxide Dismutase - metabolism; Transcription Factors - metabolism; Transcription, Genetic; Transcriptional Activation; Tumor Cells, Cultured; Tumor progression; Reactive oxygen species; Catalase; Tumor progression; Skin cancer; Oxidative stress; Skin disease; Enzyme; Rodentia; Antioxidant; Carcinogenesis; Free radical; Vertebrata; Phenotype; Mammalia; Peroxidases; Enzymatic activity; Mouse; Animal; Drug-metabolizing enzyme; Keratinocyte; Papilloma; Skin; Oxidoreductases; Benign neoplasm; Mechanism of action; Tumor cell
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(01)00656-5

We have developed an in vitro model to study the molecular mechanisms of tumor progression. Using repeated treatments with ionizing radiation or N-methyl- N′-nitro- N-nitrosoguanidine (MNNG), we caused malignant progression of a papilloma producing mouse keratinocyte cell line, 308 cells. In a previous study we have shown that the malignant variants of 308 cells have elevated reactive oxygen species (ROS) levels, and have established a functional role for the pro-oxidant state in the progressed phenotype (Carcinogenesis 20 (1999) 2063). In this study, we have evaluated the status of intracellular defense mechanisms for ROS scavenging in the progressed phenotype to identify sources that contribute to their pro-oxidant state. Our results demonstrate that a reduction in several anti-oxidant defense mechanisms, including catalase and glutathione S-transferase mu, correlates with the emergence of the malignant phenotype. We provide evidence that attenuation of catalase activity may play a functional role in the malignant progression of mouse keratinocytes.