Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/38767 http://dx.doi.org/10.1186/s12885-015-1022-6 |
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. |
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Bancovik, JasnaMoreira, Dayson F.Carrasco, DanielYao, JunPorter, DaleMoura, RicardoCamargo, AnamariaFontes-Oliveira, Cibely C.Malpartida, Miguel G.Carambula, SilviaVannier, EdouardStrauss, Bryan E.Wakamatsu, AldaAlves, Venancio A. F.Logullo, Angela F. [UNIFESP]Soares, Fernando A.Polyak, KorneliaBelizario, Jose E.Universidade de São Paulo (USP)Harvard UnivUniv Texas MD Anderson Canc CtrNovartis Inst Biomed ResHosp Sirio LibanesTufts Med CtrCanc Inst São PauloUniversidade Federal de São Paulo (UNIFESP)AC Camargo Canc Ctr2016-01-24T14:40:04Z2016-01-24T14:40:04Z2015-02-19Bmc Cancer. London: Biomed Central Ltd, v. 15, 13 p., 2015.1471-2407http://repositorio.unifesp.br/handle/11600/38767http://dx.doi.org/10.1186/s12885-015-1022-6WOS000350587200001.pdf10.1186/s12885-015-1022-6WOS:000350587200001Background: 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)NIHNovartisUniv São Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 São Paulo, SP, BrazilHarvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02215 USAUniv Texas MD Anderson Canc Ctr, Div Canc Med, Dept Neurooncol Res, Houston, TX 77030 USANovartis Inst Biomed Res, Oncol Dis Area, Cambridge, MA 02139 USANovartis Inst Biomed Res, Dev & Mol Pathways Grp, Cambridge, MA 02139 USAHosp Sirio Libanes, Ludwig Inst Canc Res, BR-01409000 São Paulo, SP, BrazilTufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA 02111 USACanc Inst São Paulo, BR-01246000 São Paulo, SP, BrazilUniv São Paulo, Sch Med, Dept Pathol, BR-05403000 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Paulista Sch Med, Dept Pathol, BR-04021001 São Paulo, SP, BrazilAC Camargo Canc Ctr, Dept Pathol, BR-01509010 São Paulo, SP, BrazilHarvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USAUniversidade Federal de São Paulo, Paulista Sch Med, Dept Pathol, BR-04021001 São Paulo, SP, BrazilFAPESP: 2001/01000-7FAPESP: 2005/56909-0Web of Science13engBiomed Central LtdBmc CancerBreast cancerDermcidinERBB signalingOncogeneApoptosisDermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signalinginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000350587200001.pdfapplication/pdf2415490${dspace.ui.url}/bitstream/11600/38767/1/WOS000350587200001.pdf14440ee89783cd585e7bc0acd1e36e12MD51open accessTEXTWOS000350587200001.pdf.txtWOS000350587200001.pdf.txtExtracted texttext/plain58220${dspace.ui.url}/bitstream/11600/38767/2/WOS000350587200001.pdf.txt55a42c1f483b90ad6827bb76ef0c60ceMD52open access11600/387672023-01-30 22:19:11.528open accessoai:repositorio.unifesp.br:11600/38767Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-01-31T01:19:11Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling |
title |
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling |
spellingShingle |
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling Bancovik, Jasna Breast cancer Dermcidin ERBB signaling Oncogene Apoptosis |
title_short |
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling |
title_full |
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling |
title_fullStr |
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling |
title_full_unstemmed |
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling |
title_sort |
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling |
author |
Bancovik, Jasna |
author_facet |
Bancovik, Jasna Moreira, Dayson F. Carrasco, Daniel Yao, Jun Porter, Dale Moura, Ricardo Camargo, Anamaria Fontes-Oliveira, Cibely C. Malpartida, Miguel G. Carambula, Silvia Vannier, Edouard Strauss, Bryan E. Wakamatsu, Alda Alves, Venancio A. F. Logullo, Angela F. [UNIFESP] Soares, Fernando A. Polyak, Kornelia Belizario, Jose E. |
author_role |
author |
author2 |
Moreira, Dayson F. Carrasco, Daniel Yao, Jun Porter, Dale Moura, Ricardo Camargo, Anamaria Fontes-Oliveira, Cibely C. Malpartida, Miguel G. Carambula, Silvia Vannier, Edouard Strauss, Bryan E. Wakamatsu, Alda Alves, Venancio A. F. Logullo, Angela F. [UNIFESP] Soares, Fernando A. Polyak, Kornelia Belizario, Jose E. |
author2_role |
author author author author author author author author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade de São Paulo (USP) Harvard Univ Univ Texas MD Anderson Canc Ctr Novartis Inst Biomed Res Hosp Sirio Libanes Tufts Med Ctr Canc Inst São Paulo Universidade Federal de São Paulo (UNIFESP) AC Camargo Canc Ctr |
dc.contributor.author.fl_str_mv |
Bancovik, Jasna Moreira, Dayson F. Carrasco, Daniel Yao, Jun Porter, Dale Moura, Ricardo Camargo, Anamaria Fontes-Oliveira, Cibely C. Malpartida, Miguel G. Carambula, Silvia Vannier, Edouard Strauss, Bryan E. Wakamatsu, Alda Alves, Venancio A. F. Logullo, Angela F. [UNIFESP] Soares, Fernando A. Polyak, Kornelia Belizario, Jose E. |
dc.subject.eng.fl_str_mv |
Breast cancer Dermcidin ERBB signaling Oncogene Apoptosis |
topic |
Breast cancer Dermcidin ERBB signaling Oncogene Apoptosis |
description |
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. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-02-19 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:40:04Z |
dc.date.available.fl_str_mv |
2016-01-24T14:40:04Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Bmc Cancer. London: Biomed Central Ltd, v. 15, 13 p., 2015. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/38767 http://dx.doi.org/10.1186/s12885-015-1022-6 |
dc.identifier.issn.none.fl_str_mv |
1471-2407 |
dc.identifier.file.none.fl_str_mv |
WOS000350587200001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1186/s12885-015-1022-6 |
dc.identifier.wos.none.fl_str_mv |
WOS:000350587200001 |
identifier_str_mv |
Bmc Cancer. London: Biomed Central Ltd, v. 15, 13 p., 2015. 1471-2407 WOS000350587200001.pdf 10.1186/s12885-015-1022-6 WOS:000350587200001 |
url |
http://repositorio.unifesp.br/handle/11600/38767 http://dx.doi.org/10.1186/s12885-015-1022-6 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Bmc Cancer |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
13 |
dc.publisher.none.fl_str_mv |
Biomed Central Ltd |
publisher.none.fl_str_mv |
Biomed Central Ltd |
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reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
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