Role of apoptosis in basal cell and squamous cell carcinoma formation
Autor: | Marion Wernli, Erwin Kump, Andrea Glaser, Peter Erb, Stanislaw A. Büchner, Jingmin Ji |
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Rok vydání: | 2005 |
Předmět: |
Fas Ligand Protein
Skin Neoplasms DNA damage Ultraviolet Rays Immunology Cell Human skin Apoptosis Biology Mice Downregulation and upregulation RNA interference medicine Immunology and Allergy Animals Humans Basal cell carcinoma Hedgehog Proteins Membrane Glycoproteins integumentary system Melanoma medicine.disease Hedgehog signaling pathway Cell biology Gene Expression Regulation Neoplastic medicine.anatomical_structure Carcinoma Basal Cell Mutation Carcinoma Squamous Cell Trans-Activators Tumor Suppressor Protein p53 DNA Damage Signal Transduction |
Zdroj: | Immunology letters. 100(1) |
ISSN: | 0165-2478 |
Popis: | Long-term ultraviolet-light (UV) exposure of human skin epidermis is associated with an increased risk for the development of skin cancers, such as melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). UV radiation not only induces DNA damage in epidermal cells, it also interferes with skin homeostasis, which is maintained by a unique distribution pattern of apoptosis-inducing and -preventing molecules. If the DNA damage is not repaired or the damaged cells are not eliminated by apoptosis, the consequence can be cell transformation, uncontrolled proliferation and eventually skin tumor formation. An important "repair" gene is the p53 suppressor gene. Excessive UV exposure can mutate the p53 gene leading to the loss of its repair function and thus apoptosis resistance of the DNA-damaged cell. For BCC formation an additional pathway has been identified. Mutation of genes of the Hedgehog signaling pathway evokes the downregulation of apoptotic genes and upregulation of anti-apoptotic genes preventing the elimination of damaged cells. In addition, BCC and SCC strongly express the apoptosis-inducing Fas-ligand (FasL) which may help the tumor to escape the attack of immune effector cells. Silencing the genes involved in tumor formation by RNA interference might become a promising new approach to treat skin tumors. |
Databáze: | OpenAIRE |
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