A neural survival factor is a candidate oncogene in breast cancer

被引:101
|
作者
Porter, D
Weremowicz, S
Chin, K
Seth, P
Keshaviah, A
Lahti-Domenici, J
Bae, YK
Monitto, CL
Merlos-Suarez, A
Chan, J
Hulette, CM
Richardson, A
Morton, CC
Marks, J
Duyao, M
Hruban, R
Gabrielson, E
Gelman, R
Polyak, K [1 ]
机构
[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[2] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[4] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA
[6] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA
[7] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA
[8] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA
[9] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA
[10] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21231 USA
[11] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[12] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA
[13] Ardais Corp, Lexington, MA 02421 USA
关键词
D O I
10.1073/pnas.1932980100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Using serial analysis of gene expression (SAGE), we identified a SAGE tag that was present only in invasive breast carcinomas and their lymph node metastases. The transcript corresponding to this SAGE tag, dermcidin (DCD), encodes a secreted protein normally expressed only in the pons of the brain and sweat glands. Array comparative genomic hybridization, fluorescence in situ hybridization, and immunohistochemical analyses determined that DCD is overexpressed in approximate to10% of invasive breast carcinomas; in some cases its overexpression is coupled with a focal copy number gain of its locus at 12q13.1, and its expression is associated with advanced clinical stage and poor prognosis. Expression of DCD in breast cancer cells promotes cell growth and survival and reduces serum dependency. Putative high- and low-affinity receptors for DCD are present on the cell surface of breast carcinomas and neurons of the brain. Based on these data we hypothesize that DCD may play a role in tumorigenesis by means of enhancing cell growth and survival in a subset of breast carcinomas.
引用
收藏
页码:10931 / 10936
页数:6
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