Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer.

作者: G Liu , A Bollig-Fischer , B Kreike , M J van de Vijver , J Abrams

DOI: 10.1038/ONC.2009.297

关键词: AmpliconDemethylaseBiologyPositional cloningCancerDemethylase activityBreast diseaseMolecular biologyBreast cancerCancer researchCarcinogenesis

摘要: Earlier, mapping of the 9p23–24 amplicon in esophageal cancer cell lines led us to positional cloning gene amplified squamous carcinoma 1 (GASC1), which encodes a nuclear protein with Jumonji C domain that catalyzes lysine (K) demethylation histones. However, transforming roles GASC1 breast remain be determined. In this study, we identified as one genes for region cancer, particularly basal-like subtypes. The levels transcript expression were significantly higher aggressive, cancers compared nonbasal-like cancers. Our vitro assays demonstrated induces transformed phenotypes, including growth factor-independent proliferation, anchorage-independent growth, altered morphogenesis Matrigel, and mammosphere forming ability, when overexpressed immortalized, nontransformed mammary epithelial MCF10A cells. Additionally, demethylase activity regulates critical stem self-renewal, NOTCH1, may linked phenotypes cancer. Thus, is driving oncogene human targeted inhibition histone could provide potential new avenues therapeutic development.

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