A neural survival factor is a candidate oncogene in breast cancer.
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 approximately 10% 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.
Porter
Dale
D
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Weremowicz
Stanislawa
S
Chin
Koei
K
Seth
Pankaj
P
Keshaviah
Aparna
A
Lahti-Domenici
Jaana
J
Bae
Young Kyung
YK
Monitto
Constance L
CL
Merlos-Suarez
Ana
A
Chan
Jennifer
J
Hulette
Christine M
CM
Richardson
Andrea
A
Morton
Cynthia C
CC
Marks
Jeffrey
J
Duyao
Mabel
M
Hruban
Ralph
R
Gabrielson
Edward
E
Gelman
Rebecca
R
Polyak
Kornelia
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm; D020869:Gene Expression Profiling; D006801:Humans; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009857:Oncogenes; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm