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Successful development of squamous cell carcinoma and hyperplasia in RGEN-mediated p27 KO mice after the treatment of DMBA and TPA

Laboratory Animal Research volume 34, pages 118–125 (2018)Cite this article

Abstract

To evaluate the carcinogenicity of p27 knockout (KO) mice with RNA-guided endonuclease (RGENs)-mediated p27 mutant exon I gene (IΔ), alterations in the carcinogenic phenotypes including tumor spectrum, tumor suppressor proteins, apoptotic proteins and cell cycle regulators were observed in p27 (IΔ) KO mice after treatment with 7,12-Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)(DT) for 5 months. The target region (544~571 nt) in exon I of the p27 gene was successfully disrupted in p27 (IΔ) KO mice using the RGEN-induced non-homologous end joining (NHEJ) technique. After DT exposure for 5 months, a few solid tumors (identified as squamous cell carcinoma) developed on the surface of back skin of DT-treated p27 (IΔ) KO mice. Also, squamous cell hyperplasia with chronic inflammation was detected in the skin dermis of DT-treated p27 (IΔ) KO mice, while the Vehicle+p27 (IΔ) KO mice and WT mice maintained their normal histological skin structure. A significant increase was observed in the expression levels of tumor suppressor protein (p53), apoptotic proteins (Bax, Bcl-2 and Caspase-3) and cell-cycle regulator proteins (Cyclin D1, CDK2 and CDK4) in the skin of DT-treated p27 (IΔ) KO mice, although their enhancement ratio was varied. Taken together, the results of the present study suggest that squamous cell carcinoma and hyperplasia of skin tissue can be successfully developed in new p27 (IΔ) KO mice produced by RGEN-induced NHEJ technique following DT exposure for 5 months.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biomaterials Science, College of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, 50 Cheonghak-ri, Samnangjineup Miryang-si, Gyeongsangnam-do, 627-706, Korea

    Jun Young Choi, Woo Bin Yun, Ji Eun Kim, Mi Rim Lee, Jin Ju Park, Bo Ram Song, Hye Ryeong Kim, Ji Won Park, Mi Ju Kang & Dae Youn Hwang (Professor and Vice Dean)

  2. Department of Experimental Animal Research, Clinical Research Institute, Seoul National University Hospital, Korea

    Byeong Cheol Kang

  3. Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Korea

    Han-Woong Lee

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  1. Jun Young Choi
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Correspondence to Dae Youn Hwang.

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Choi, J.Y., Yun, W.B., Kim, J.E. et al. Successful development of squamous cell carcinoma and hyperplasia in RGEN-mediated p27 KO mice after the treatment of DMBA and TPA. Lab Anim Res 34, 118–125 (2018). https://doi.org/10.5625/lar.2018.34.3.118

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  • DOI: https://doi.org/10.5625/lar.2018.34.3.118

Keywords

Laboratory Animal Research

ISSN: 2233-7660