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Published on: October 11, 2019
Expression of nuclear factor erythroid 2 protein in malignant cutaneous tumors
Chang Yong Choi1, Jin Young Kim1, Seo Yeong Wee1
1Department of Plastic and Reconstructive Surgery, Soonchunhyang Gumi Hospital, Soonchunhyang University College of Medicine, Gumi, Korea.
Background:
Reactive oxygen species (ROS) damages cell molecules, and modifies cell signaling. The nuclear factor E2-related factor (Nrf2) is a critical transcription regulator, which protects cells against oxidative damage. Nrf2 expression is increased in a large number of cancers. However, little information has been reported regarding the expression of Nrf2 in skin cancers. Hence, we explored the expression of Nrf2 protein in skin cancers.
Methods:
The Nrf2 protein expression in 24 specimens, including 6 malignant melanomas (MM), 6 squamous cell carcinomas (SCC), 6 basal cell carcinomas (BCC), and 6 normal skin tissues, was evaluated by western blotting. Immunohistochemical staining was performed. The expression of Kelch-like ECH-associated protein 1 (Keap1), the key regulator of Nrf2, was also analyzed by western blotting.
Results:
Small interfering RNA transfection to the melanoma cell line G361 confirmed that an approximately 66 kDa band was the true Nrf2 band. The western blot revealed that the Nrf2 protein was definitely expressed in normal skin tissues, but the Nrf2 expression was decreased in MM, SCC, and BCC. Immunohistochemical examination showed that expression of Nrf2 was decreased in all skin cancer tissues compared to the normal skin tissues. Keap1 was not expressed in all malignant skin tumors and normal skin tissues by western blot.
Conclusions:
ROS was increased in various types of cancers which proteins were highly expressed or underexpressed. This study demonstrated that the expression of Nrf2 protein was down-regulated in human malignant skin tumors. We suggest that decreased expression of Nrf2 is related to skin cancers.
Insights
Nuclear factor E2-related factor (Nrf2) protects against oxidative damage. This study found decreased Nrf2 protein expression in malignant melanoma, squamous cell carcinoma, and basal cell carcinoma, suggesting a link to skin cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Reactive oxygen species (ROS) cause cellular damage and alter signaling.
- Nuclear factor E2-related factor (Nrf2) is a key regulator protecting cells from oxidative stress.
- Nrf2 is upregulated in many cancers, but its role in skin cancers is under-investigated.
Purpose of the Study:
- To investigate the expression of Nrf2 protein in various human skin cancers.
- To compare Nrf2 levels in malignant melanoma, squamous cell carcinoma, and basal cell carcinoma with normal skin tissues.
Main Methods:
- Western blotting and immunohistochemical staining were used to analyze Nrf2 protein expression.
- The study included 24 specimens: 6 malignant melanomas (MM), 6 squamous cell carcinomas (SCC), 6 basal cell carcinomas (BCC), and 6 normal skin samples.
- Expression of Kelch-like ECH-associated protein 1 (Keap1), a key Nrf2 regulator, was also assessed.
Main Results:
- Nrf2 protein was confirmed and detected in normal skin tissues.
- Nrf2 expression was significantly decreased in all examined skin cancer types (MM, SCC, BCC) compared to normal skin.
- Keap1 showed no expression in either malignant skin tumors or normal skin tissues via western blot.
Conclusions:
- The study demonstrates down-regulation of Nrf2 protein in human malignant skin tumors.
- Decreased Nrf2 expression is suggested to be associated with the pathogenesis of skin cancers.
- Further research into the role of Nrf2 in skin cancer is warranted.
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