1. Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene
- Author
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Timothy Hoey, Ken C. Q. Nguyen, Lori Spiegel, W. Richard McCombie, Liyun Chen, Clifford Yen, Lin Pei, Scott Powers, Jeffrey R. Marks, Christina M Koch, James Jiayuan Tong, Yue Peng, Scott W. Lowe, Lily Yeh Jan, Xi-Ping Zhang, Michael Wigler, Lei-Hoon See, Allyson Servoss, and David Mu
- Subjects
Cancer Research ,Potassium Channels ,Cell Transplantation ,Molecular Sequence Data ,Transplantation, Heterologous ,Breast Neoplasms ,Biology ,Cell Line ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Breast cancer ,Gene duplication ,medicine ,Animals ,Humans ,skin and connective tissue diseases ,030304 developmental biology ,Sequence Tagged Sites ,Regulation of gene expression ,0303 health sciences ,Genome, Human ,Gene Amplification ,Cancer ,Oncogenes ,Cell Biology ,Amplicon ,medicine.disease ,Physical Chromosome Mapping ,Molecular biology ,3. Good health ,Transplantation ,Gene Expression Regulation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,Chromosomal region ,Cancer research ,Female ,Representational difference analysis ,DNA Probes ,Chromosomes, Human, Pair 8 - Abstract
Representational difference analysis (RDA) of human breast cancer was used to discover a novel amplicon located at chromosomal region 8q24.3. We examined a series of breast cancer samples harboring amplification of this region and determined that KCNK9 is the sole overexpressed gene within the amplification epicenter. KCNK9 encodes a potassium channel that is amplified from 3-fold to 10-fold in 10% of breast tumors and overexpressed from 5-fold to over 100-fold in 44% of breast tumors. Overexpression of KCNK9 in cell lines promotes tumor formation and confers resistance to both hypoxia and serum deprivation, suggesting that its amplification and overexpression plays a physiologically important role in human breast cancer.
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