Jiang Hui , Zhang Juan , Xu Dan , He Li . Construction of UV-induced Skin Squamous Cell Carcinoma Model of SKH-1 Hairless Mice and Expression of DNA-PKcs in Mice and Adult Squamous Cell Carcinoma[J]. Journal of Kunming Medical University, 2019, 40(03): 11-17.
Citation: Jiang Hui , Zhang Juan , Xu Dan , He Li . Construction of UV-induced Skin Squamous Cell Carcinoma Model of SKH-1 Hairless Mice and Expression of DNA-PKcs in Mice and Adult Squamous Cell Carcinoma[J]. Journal of Kunming Medical University, 2019, 40(03): 11-17.

Construction of UV-induced Skin Squamous Cell Carcinoma Model of SKH-1 Hairless Mice and Expression of DNA-PKcs in Mice and Adult Squamous Cell Carcinoma

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基金: 国家自然科学基金资助项目 (81472540, 81660518); 昆明医科大学硕士研究生创新基金资助项目 (2018S092);

  • Received Date: 2018-11-06
  • Objective To construct an animal model of squamous cell carcinoma of the skin in SKH-1 mice with ultraviolet irradiation, and to investigate the DNA-PKcs activation level of DNA-PKcs-m TORC2/Akt signal transduction pathway during UV-induced skin SCC and AK to SCC transformation. Methods 43 SKH-l hairless mice were randomly divided into experimental group (33) and control group (10) .The experimental group used the SUV-1000 solar simulator to simulate sun-irradiated SKH-1 hairless mice, and the control group did not intervene. Experimental group 1 maintained irradiation for 24 weeks, and experimental group 2 maintained irradiation for 16 weeks. The mice were sacrificed at 12, 18, 24, and 28 weeks for skin histopathological examination. At 28 weeks, the same skin of the same mouse was taken for histopathological examination and immunohistochemistry.Five cases of adult solar keratosis (AK) , cutaneous squamous cell carcinoma (SCC) , normal light-protected site (NNS) , and normal exposed site (NES) were collected for Western Blot. Results After 12 weeks, some mice in the experimental group were thickened in the back skin. At 17 weeks, the papules with diameter ≥ 1 mm appeared in the back skin of experimental group. After 28 weeks of irradiation, the tumor formation rate reached100%. No tumor formation was observed in the control group. Both DNA-PKcs and p-DNA-PKcs (T2609) were localized in the cytoplasm and nucleus. Expression of DNA-PKcs increased in epidermal tissue. There was a difference in the statistical analysis of DNA-PKcs expression (P<0.05) , but there was no difference in the expression of p-DNA-PKcs (T2609) (P>0.05) .The expression levels of DNA-PKcs and p-DNA-PKcs (T2609) in human epidermal tissue increased and there were statistical differences (P<0.05) .Conclusions We successfulyl prepared of mouse AK model and SCC model. It is clear that UV-induced squamous cell carcinoma of the skin can induce DNA damage and repair.
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  • [1]
    [1]ROGERS H W, WEINSTOCK M A, HARRIS A R, et al.Incidence estimate of nonmelanoma skin cancer in the United States, 2006[J].Archives of Dermatology, 2010, 146 (3) :283-287.
    [2]
    [2]DONALDSON M R, COLDIRON B M. No end in sight:the skin cancer epidemic continues[J].Seminars in Cutaneous Medicine and Surgery, 2011, 30 (1) :3-5.
    [3]
    [3]DIKA E, FANTI P A, MISCIALI C, et al. Risk of skin cancer development in 672 patients affected by actinic keratosis.Giornaleitaliano di dermatologia e venereologia:organoufficiale[J].Societaitaliana di Dermatologia E Sifilografia, 2016, 151 (6) :628-633.
    [4]
    [4]RASTOGI R P, RICHA, KUMAR A, et al. Molecular mechanisms of ultraviolet radiation-induced DNA damage and repair[J].Journal of Nucleic Acids, 2010, 16 (2010) :1-32.
    [5]
    [5]WANG Y N, FANG H, WANG H M, et al. Effect of chronic exposure to ultraviolet on skin barrier function[J].Medical Sciences, 2010, 39 (5) :517-522.
    [6]
    [6]SALASCHE S J. Epidemiology of actinic keratoses and squamous cell carcinoma[J].Journal of the American Academy of Dermatology, 2000, 42 ( (1 Pt 2) :4-7.
    [7]
    [7]KATIYAR S K. Dietary proanthocyanidins inhibit UV radiation-induced skin tumor development through functional activation of the immune system[J].Molecular Nutrition&Food Research, 2016, 60 (6) :1374-1382.
    [8]
    [8]D'ORAZIO J, JARRETT S, AMARO-ORTIZ A, et al. UV radiation and the skin[J].International Journal of Molecular Sciences, 2013, 14 (6) :12222-12248.
    [9]
    [9]JETTE N, LEES-MILLER S P. The DNA-dependent protein kinase:A multifunctional protein kinase with roles in DNA double strand break repair and mitosis[J].Progress in Biophysics and Molecular Biology, 2015, 117 (2-3) :194-205.
    [10]
    [10]DOUGLAS P, YE R, TRINKLE-MULCAHY L, et al.Polo-like kinase 1 (PLK1) and protein phosphatase 6 (PP6) regulate DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation in mitosis[J].Bioscience Reports, 2014, 34 (3) :257-271.
    [11]
    [11]GOODWIN J F, KOTHARI V, DRAKE J M, et al.DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis[J].Cancer cell, 2015, 28 (1) :97-113.
    [12]
    [12]SONE K, PIAO L, NAKAKIDO M, et al. Critical role of lysine 134 methylation on histone H2AX for gamma-H2AX production and DNA repair[J].Nature Communications, 2014, 5 (1) :1-12.
    [13]
    [13]TU Y, JI C, YANG B, et al. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) -SIN1 association mediates ultraviolet B (UVB) -induced Akt Ser-473 phosphorylation and skin cell survival[J].Molecular Cancer, 2013, 12 (1) :172.
    [14]
    [14]FLORENCE M E, MASSUDA J Y, SOARES T C, et al.p53immunoexpression in stepwise progression of cutaneous squamous cell carcinoma and correlation with angiogenesis and cellular proliferation[J].Pathology, Research and Practice, 2015, 211 (10) :782-788.
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