A neural survival factor is a candidate oncogene in breast cancer

Dale Porter, Stanislawa Weremowicz, Koei Chin, Pankaj Seth, Aparna Keshaviah, Jaana Lahti-Domenici, Young Kyung Bae, Constance L. Monitto, Ana Merlos-Suarez, Jennifer Chan, Christine M. Hulette, Andrea Richardson, Cynthia C. Morton, Jeffrey Marks, Mabel Duyao, Ralph Hruban, Edward Gabrielson, Rebecca Gelman, Kornelia Polyak

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95 Scopus citations

Abstract

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 ≈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.

Original languageEnglish (US)
Pages (from-to)10931-10936
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number19
DOIs
StatePublished - Sep 16 2003

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    Porter, D., Weremowicz, S., Chin, K., Seth, P., Keshaviah, A., Lahti-Domenici, J., Bae, Y. K., Monitto, C. L., Merlos-Suarez, A., Chan, J., Hulette, C. M., Richardson, A., Morton, C. C., Marks, J., Duyao, M., Hruban, R., Gabrielson, E., Gelman, R., & Polyak, K. (2003). A neural survival factor is a candidate oncogene in breast cancer. Proceedings of the National Academy of Sciences of the United States of America, 100(19), 10931-10936. https://doi.org/10.1073/pnas.1932980100