title: The oncogenic role of GASC1 in chemically induced mouse skin cancer.
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.
authors.affiliation: Department of Dermatology, Nihon University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ozaki
authors.affiliation: 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.|Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan. fujiwara.kyoko@nihon-u.ac.jp.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Division of Public Health, Department of Social Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Department of Dermatology, Nihon University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Terui
authors.affiliation: Division of General Medicine, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi, Tokyo, 173-8610, Japan.|Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.affiliation: Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba, Japan. hnagase@chiba-cc.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009857:Oncogenes; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D047368:Tumor Burden
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene; C544194:Jmjd2c protein, mouse; D056484:Jumonji Domain-Containing Histone Demethylases