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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Cypermethrin exposure leads to regulation of proteins expression involved in neoplastic transformation in mouse skin
Jasmine George1, Amit Kumar Srivastava, Richa Singh
1Proteomics Laboratory, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, India.
Abstract:
Cypermethrin, a synthetic pyrethroid insecticide is shown to exert carcinogenic effects in rodents; however, its underlying mechanism remains elusive. Here, we showed the effect of cypermethrin on protein expression involved in neoplastic transformation in mouse skin. Comparative protein expression profiles between untreated control and cypermethrin-treated mouse skin were explored using 2-DE. A total of 27 spots that were statistically significant (p<0.05) and differentially expressed in response to cypermethrin exposure were identified by MALDI-TOF/TOF and LC-MS/MS. Among them, six up-regulated proteins (carbonic anhydrase 3 (Ca 3), Hsp-27, S100A6, galectin-7, S100A9, S100A11) and one down-regulated protein (superoxide dismutase [Cu-Zn] (Sod 1)) are associated with cancer-related key processes. These selected dysregulated proteins were further validated in 2-DE gels of mouse skin treated with known tumorigens (benzo-[a]-pyrene, 12-O-tetradecanoyl-phorbol-13-acetate and mezerein), respectively. Comparative studies showed that Ca 3, S100A6, S100A9, S100A11 and Sod 1 are specific for stages of development and progression of tumors whereas Hsp-27 and galectin-7 are specific for tumor promotion stage by cypermethrin in mouse skin. Furthermore, these chosen proteins confirmed by Western blotting and immunofluorescence staining were consistent with changes in 2-DE check. This proteomic investigation for the first time provides key proteins that will contribute in understanding the mechanism behind cypermethrin-induced neoplastic transformation.
Insights
Cypermethrin exposure alters protein expression in mouse skin, potentially driving cancer development. This study identifies key proteins involved in cypermethrin-induced neoplastic transformation, offering insights into its carcinogenic mechanisms.
Area of Science:
- Proteomics
- Toxicology
- Cancer Research
Background:
- Cypermethrin, a pyrethroid insecticide, exhibits carcinogenic effects in rodents.
- The precise molecular mechanisms underlying cypermethrin's carcinogenicity remain largely unknown.
Purpose of the Study:
- To investigate the impact of cypermethrin on protein expression in mouse skin.
- To identify proteins involved in cypermethrin-induced neoplastic transformation.
Main Methods:
- Comparative proteomic analysis using 2-DE to compare cypermethrin-treated and untreated mouse skin.
- Protein identification via MALDI-TOF/TOF and LC-MS/MS.
- Validation of key proteins using Western blotting and immunofluorescence staining.
Main Results:
- 27 differentially expressed protein spots were identified in response to cypermethrin.
- Six proteins (Ca 3, Hsp-27, S100A6, galectin-7, S100A9, S100A11) were upregulated, and one (Sod 1) was downregulated.
- Specific proteins were linked to tumor development, progression, or promotion stages.
Conclusions:
- This proteomic study identifies critical proteins associated with cypermethrin-induced neoplastic transformation.
- The findings provide novel insights into the molecular mechanisms of cypermethrin's carcinogenic effects.
- Identified proteins serve as potential biomarkers for cypermethrin-induced skin carcinogenesis.
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