Abstract
Gene amplified in squamous cell carcinoma (SCC) 1 (GASC1), also known as KDM4C/JMJD2C, encodes a histone demethylase that specifically demethylates lysine residues (H3K9, H3K36, and H1.4K26) and plays a crucial role in the regulation of gene expression as well as in heterochromatin formation. GASC1 is located at human chromosome 9p23–24, where frequent genomic amplification is observed in human esophageal cancer, and its aberrant expression is detected in a variety of human cancers, such as breast, colon, and prostate. Therefore, it is highly likely that GASC1 contributes to the genesis and/or development of cancer. However, there is a lack of direct evidence of GASC1 having an oncogenic function. In this study, we aimed to clarify the role of GASC1 in the skin SCC carcinogenesis. For this purpose, we generated Gasc1-heterozygous mice (Gasc1 +/−) with reduced expression of Gasc1. On the basis of our results, Gasc1 +/− mice displayed a significantly lower incidence and multiplicity of both benign and malignant tumors induced by the two-stage skin carcinogenesis protocol than wild-type mice. In addition, the volume of carcinoma was significantly lower in Gasc1 +/− mice. Consistent with these observations, knocking down of Gasc1 resulted in reduced cell viability of SCC cells in vitro. Our findings clearly demonstrated that GASC1 has an oncogenic role in skin carcinogenesis.
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Acknowledgments
We thank Mr. M. Kataba, Ms. A. Oguni, and Mr. J. Igarashi for their technical support and Ms. K. Takgata for her secretarial assistance. This work was supported in part by MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2011–2015) to Kyoko Fujiwara, Tadashi Terui, Masayoshi Soma and Hiroki Nagase, by JSPS KAKENHI Grant Number 24591637, 15K09791 to Kyoko Fujiwara and Tadashi Terui, by the Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation to Johji Inazawa and the New Energy and Industrial Technology Development Organization (NEDO) to Johji Inazawa.
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Supplementary material 1. Supplementary Figure S1 Body weights of wild-type and Gasc1 +/− mice. None of the animals used in this analysis were treated with DMBA and TPA. Their body weights were measured every 2 weeks from 4 weeks of age up to 56 weeks (TIFF 45 kb)
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Ozaki, Y., Fujiwara, K., Ikeda, M. et al. The oncogenic role of GASC1 in chemically induced mouse skin cancer. Mamm Genome 26, 591–597 (2015). https://doi.org/10.1007/s00335-015-9592-9
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DOI: https://doi.org/10.1007/s00335-015-9592-9