Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling

Autor(es):Mostrar menos -

Bancovik, Jasna ^[1] ; Moreira, Dayson F. ^[1] ; Carrasco, Daniel ^[2] ; Yao, Jun ^[3] ; Porter, Dale ^{[4, 5]} ; Moura, Ricardo ^[6] ; Camargo, Anamaria ^[6] ; Fontes-Oliveira, Cibely C. ^[1] ; Malpartida, Miguel G. ^[1] ; Carambula, Silvia ^[7] ; Vannier, Edouard ^[7] ; Strauss, Bryan E. ^[8] ; Wakamatsu, Alda ^[9] ; Alves, Venancio A. F. ^[9] ; Logullo, Angela F. ^[10] ; Soares, Fernando A. ^[11] ; Polyak, Kornelia ^[12] ; Belizario, Jose E. ^[1]

Afiliação do(s) autor(es):Mostrar menos -

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo, SP - Brazil

^[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02215 - USA

^[3] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Neurooncol Res, Houston, TX 77030 - USA

^[4] Novartis Inst Biomed Res, Oncol Dis Area, Cambridge, MA 02139 - USA

^[5] Novartis Inst Biomed Res, Dev & Mol Pathways Grp, Cambridge, MA 02139 - USA

^[6] Hosp Sirio Libanes, Ludwig Inst Canc Res, BR-01409000 Sao Paulo, SP - Brazil

^[7] Tufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA 02111 - USA

^[8] Canc Inst Sao Paulo, BR-01246000 Sao Paulo, SP - Brazil

^[9] Univ Sao Paulo, Sch Med, Dept Pathol, BR-05403000 Sao Paulo, SP - Brazil

^[10] Univ Fed Sao Paulo, Paulista Sch Med, Dept Pathol, BR-04021001 Sao Paulo, SP - Brazil

^[11] AC Camargo Canc Ctr, Dept Pathol, BR-01509010 Sao Paulo, SP - Brazil

^[12] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 - USA

• Tipo de documento: Artigo Científico
• Fonte: BMC CANCER; v. 15, FEB 19 2015.
• Citações Web of Science: 7

Resumo

Background: We previously identified dermicidin (DCD), which encodes a growth and survival factor, as a gene amplified and overexpressed in a subset of breast tumors. Patients with DCD-positive breast cancer have worse prognostic features. We therefore searched for specific molecular signatures in DCD-positive breast carcinomas from patients and representative cell lines. Methods: DCD expression was evaluated by qRT-PCR, immunohistochemical and immunoblot assays in normal and neoplastic tissues and cell lines. To investigate the role of DCD in breast tumorigenesis, we analyzed the consequences of its downregulation in human breast cancer cell lines using three specific shRNA lentiviral vectors. Genes up- and down-regulated by DCD were identified using Affymetrix microarray and analyzed by MetaCore Platform. Results: We identified DCD splice variant (DCD-SV) that is co-expressed with DCD in primary invasive breast carcinomas and in other tissue types and cell lines. DCD expression in breast tumors from patients with clinical follow up data correlated with high histological grade, HER2 amplification and luminal subtype. We found that loss of DCD expression led to reduced cell proliferation, resistance to apoptosis, and suppressed tumorigenesis in immunodeficient mice. Network analysis of gene expression data revealed perturbed ERBB signaling following DCD shRNA expression including changes in the expression of ERBB receptors and their ligands. Conclusions: These findings imply that DCD promotes breast tumorigenesis via modulation of ERBB signaling pathways. As ERBB signaling is also important for neural survival, HER2+ breast tumors may highjack DCD's neural survival-promoting functions to promote tumorigenesis. (AU)

• Processo FAPESP: 01/01000-7 - Análise da expressão de genes e proteínas e da atividade de enzimas caspases em células do músculo esquelético durante a caquexia induzida por tumores malignos e citocinas
• Beneficiário: José Ernesto Belizario
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 05/56909-0 - Avaliacao do potencial oncogenico da proteina pif/dcd e da variante pif-sv.
• Beneficiário: José Ernesto Belizario
• Modalidade de apoio: Auxílio à Pesquisa - Regular