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Mamm Genome. 2015 Dec;26(11-12):591-7. doi: 10.1007/s00335-015-9592-9. Epub 2015 Aug 7.

The oncogenic role of GASC1 in chemically induced mouse skin cancer.

Author information

1
Department of Dermatology, Nihon University Graduate School of Medicine, Tokyo, Japan.
2
Division of General Medicine, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi, Tokyo, 173-8610, Japan. fujiwara.kyoko@nihon-u.ac.jp.
3
Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan. fujiwara.kyoko@nihon-u.ac.jp.
4
Division of Public Health, Department of Social Medicine, Nihon University School of Medicine, Tokyo, Japan.
5
Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba, Japan.
6
Division of General Medicine, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi, Tokyo, 173-8610, Japan.
7
Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan.
8
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
9
Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba, Japan. hnagase@chiba-cc.jp.

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.

PMID:
26248577
DOI:
10.1007/s00335-015-9592-9
[Indexed for MEDLINE]

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