The role of peroxisome proliferator-activated receptor-coactivator-1(pgc-1) gene in prevention of skin cancer

Skin cancer is a common and abnormal development of cells of the skin. There are three main types of skin cancer including basal cell carcinoma, squamous cell carcinoma, and melanoma which originates from the pigment-producing skin cells (melanocytes) and is more disastrous than the first two. The most important risk factors for skin cancer are UV exposure, suppressed immune system, ionizing radiation and etc. Naturally, Ultraviolet light -exposed keratinocytes secrete α-MSH which activates melanin formation in melanocytes by inducing the microphthalmia-associated transcription factor(MITF). PPAR-γ coactivator (PGC)-1α and PGC-1β are a part of a small family of transcriptional coactivators and constituent of melanogenic system, as activate the MITF promoter. PGC-1 connects transcription factors with the general transcription apparatus and increases transcription. Also, PGC-1 has the role in multiple metabolic pathways such as activating mtDNA replication and transcription byinteracting with NRF-1 and NRF-2 factors of mitochondria and has the positive role in mitochondrial biogenesis in different organs such as skin. PGC-1 is highly expressed and induced by cold or adrenergic stimuli as exposure to cold temperatures motivates mitochondrial proliferation. Several study have showed that blockage of PGC-1α and PGC-1β inhibits the α-MSH-mediated induction ofMITF and melanogenic system whereas overexpression of them increases pigment formation in cell culture and transgenic animals. With regard to role of PGC-1 coactivators as regulators of humantanning and producing pigments and the protective role of pigments against skin cancers, it is seem that more excitation and high expression of PGC-1 gene by different methods such as using of supplements like Panax ginseng root extract, pomegranate fruit extract or specific creams could regulate mitochondrial synthesis and melanogenesis in skin cells and protect humans from melanoma in high risk region by increasing key transcriptional factors such as AMP-activated protein kinase, PGC-1 alpha, NRF-2. Hence, the further searches are needed for generating more effective products andcomponents in order to express highly PGC-1 and enhance skin resistance against cancer.

کلیدواژه ها:

Skin Cancer ، Cancer Prevention ، Gene and Cancer ، Cancer Treatment and Management ، Targeted Cancer Therapy ، Drugs and Cancer