Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene

被引:205
作者
Mu, D
Chen, LY
Zhang, XP
See, LH
Koch, CM
Yen, C
Tong, JJ
Spiegel, L
Nguyen, KCQ
Servoss, A
Peng, Y
Pei, L
Marks, JR
Lowe, S
Hoey, T
Jan, LY
McCombie, WR
Wigler, MH
Powers, S
机构
[1] Tularik Inc, Genom Div, Greenlawn, NY 11740 USA
[2] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
[3] Tularik Inc, San Francisco, CA 94080 USA
[4] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA
[5] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
[6] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA
[7] Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA
关键词
D O I
10.1016/S1535-6108(03)00054-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:297 / 302
页数:6
相关论文
共 25 条
[1]   Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene [J].
Albertson, DG ;
Ylstra, B ;
Segraves, R ;
Collins, C ;
Dairkee, SH ;
Kowbel, D ;
Kuo, WL ;
Gray, JW ;
Pinkel, D .
NATURE GENETICS, 2000, 25 (02) :144-146
[2]  
Chapman CG, 2000, MOL BRAIN RES, V82, P74
[3]   Positional cloning of ZNF217 and NABC1:: Genes amplified at 20q13.2 and overexpressed in breast carcinoma [J].
Collins, C ;
Rommens, JM ;
Kowbel, D ;
Godfrey, T ;
Tanner, M ;
Hwang, S ;
Polikoff, D ;
Nonet, G ;
Cochran, J ;
Myambo, K ;
Jay, KE ;
Froula, J ;
Cloutier, T ;
Kuo, WL ;
Yaswen, P ;
Dairkee, S ;
Giovanola, J ;
Hutchinson, GB ;
Isola, J ;
Kallioniemi, OP ;
Palazzolo, M ;
Martin, C ;
Ericsson, C ;
Pinkel, D ;
Albertson, D ;
Li, WB ;
Gray, JW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (15) :8703-8708
[4]   Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours [J].
Graeber, TG ;
Osmanian, C ;
Jacks, T ;
Housman, DE ;
Koch, CJ ;
Lowe, SW ;
Giaccia, AJ .
NATURE, 1996, 379 (6560) :88-91
[5]   LUMEN FORMATION BY EPITHELIAL-CELL LINES IN RESPONSE TO COLLAGEN OVERLAY - A MORPHOGENETIC MODEL IN CULTURE [J].
HALL, HG ;
FARSON, DA ;
BISSELL, MJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (15) :4672-4676
[6]   Combined antisense and pharmacological approaches implicate hTASK as an airway O2 sensing K+ channel [J].
Hartness, ME ;
Lewis, A ;
Searle, GJ ;
O'Kelly, I ;
Peers, C ;
Kemp, PJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (28) :26499-26508
[7]  
Hiemstra J L, 1994, Prog Clin Biol Res, V385, P51
[8]   TASK-3, a new member of the tandem pore K+ channel family [J].
Kim, Y ;
Bang, H ;
Kim, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (13) :9340-9347
[9]   Tissue microarrays for high-throughput molecular profiling of tumor specimens [J].
Kononen, J ;
Bubendorf, L ;
Kallioniemi, A ;
Bärlund, M ;
Schraml, P ;
Leighton, S ;
Torhorst, J ;
Mihatsch, MJ ;
Sauter, G ;
Kallioniemi, OP .
NATURE MEDICINE, 1998, 4 (07) :844-847
[10]   Suppression of tumor growth through disruption of hypoxia-inducible transcription [J].
Kung, AL ;
Wang, S ;
Klco, JM ;
Kaelin, WG ;
Livingston, DM .
NATURE MEDICINE, 2000, 6 (12) :1335-1340