HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer

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dc.contributor.authorDa Silva, Leonard [UNIFESP]
dc.contributor.authorSimpson, Peter T.
dc.contributor.authorSmart, Chanel E.
dc.contributor.authorCocciardi, Sibylle
dc.contributor.authorWaddell, Nic
dc.contributor.authorLane, Annette
dc.contributor.authorMorrison, Brian J.
dc.contributor.authorVargas, Ana Cristina
dc.contributor.authorHealey, Sue
dc.contributor.authorBeesley, Jonathan
dc.contributor.authorPakkiri, Pria
dc.contributor.authorParry, Suzanne
dc.contributor.authorKurniawan, Nyoman
dc.contributor.authorReid, Lynne
dc.contributor.authorKeith, Patricia
dc.contributor.authorFaria, Paulo
dc.contributor.authorPereira, Emilio
dc.contributor.authorSkalova, Alena
dc.contributor.authorBilous, Michael
dc.contributor.authorBalleine, Rosemary L.
dc.contributor.authorDo, Hongdo
dc.contributor.authorDobrovic, Alexander
dc.contributor.authorFox, Stephen
dc.contributor.authorFranco, Marcello [UNIFESP]
dc.contributor.authorReynolds, Brent
dc.contributor.authorKhanna, Kum Kum
dc.contributor.authorCummings, Margaret
dc.contributor.authorChenevix-Trench, Georgia
dc.contributor.authorLakhani, Sunil R.
dc.contributor.institutionUniv Queensland
dc.contributor.institutionQueensland Inst Med Res
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionGriffith Univ
dc.contributor.institutionEijkman Inst
dc.contributor.institutionInst Nacl Canc
dc.contributor.institutionLab Salomao & Zoppi
dc.contributor.institutionCharles Univ Prague
dc.contributor.institutionUniv Sydney
dc.contributor.institutionPeter MacCallum Canc Ctr
dc.contributor.institutionRoyal Brisbane & Womens Hosp
dc.date.accessioned2016-01-24T13:59:02Z
dc.date.available2016-01-24T13:59:02Z
dc.date.issued2010-01-01
dc.description.abstractIntroduction: Metastases to the brain from breast cancer have a high mortality, and basal-like breast cancers have a propensity for brain metastases. However, the mechanisms that allow cells to colonize the brain are unclear.Methods: We used morphology, immunohistochemistry, gene expression and somatic mutation profiling to analyze 39 matched pairs of primary breast cancers and brain metastases, 22 unmatched brain metastases of breast cancer, 11 non-breast brain metastases and 6 autopsy cases of patients with breast cancer metastases to multiple sites, including the brain.Results: Most brain metastases were triple negative and basal-like. the brain metastases over-expressed one or more members of the HER family and in particular HER3 was significantly over-expressed relative to matched primary tumors. Brain metastases from breast and other primary sites, and metastases to multiple organs in the autopsied cases, also contained somatic mutations in EGFR, HRAS, KRAS, NRAS or PIK3CA. This paralleled the frequent activation of AKT and MAPK pathways. in particular, activation of the MAPK pathway was increased in the brain metastases compared to the primary tumors.Conclusions: Deregulated HER family receptors, particularly HER3, and their downstream pathways are implicated in colonization of brain metastasis. the need for HER family receptors to dimerize for activation suggests that tumors may be susceptible to combinations of anti-HER family inhibitors, and may even be effective in the absence of HER2 amplification (that is, in triple negative/basal cancers). However, the presence of activating mutations in PIK3CA, HRAS, KRAS and NRAS suggests the necessity for also specifically targeting downstream molecules.en
dc.description.affiliationUniv Queensland, Clin Res Ctr, Brisbane, Qld 4029, Australia
dc.description.affiliationQueensland Inst Med Res, Brisbane, Qld 4006, Australia
dc.description.affiliationUniversidade Federal de São Paulo, EPM, Dept Anat Patol, BR-04024000 São Paulo, Brazil
dc.description.affiliationGriffith Univ, Brisbane, Qld 4011, Australia
dc.description.affiliationUniv Queensland, Ctr Magnet Resonance, Brisbane, Qld 4072, Australia
dc.description.affiliationEijkman Inst, Jakarta 10430, Indonesia
dc.description.affiliationInst Nacl Canc, Dept Patol, BR-20230130 Rio de Janeiro, Brazil
dc.description.affiliationLab Salomao & Zoppi, Dept Patol, BR-04104000 São Paulo, Brazil
dc.description.affiliationCharles Univ Prague, Fac Med, Dept Pathol, Plzen 30605, Czech Republic
dc.description.affiliationUniv Sydney, Inst Clin Pathol & Med Res, Sydney W Area Hlth Serv, Sydney, NSW 2145, Australia
dc.description.affiliationUniv Sydney, Westmead Millennium Inst, Sydney W Area Hlth Serv, Sydney, NSW 2145, Australia
dc.description.affiliationPeter MacCallum Canc Ctr, Dept Pathol, Melbourne, Vic 3002, Australia
dc.description.affiliationUniv Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia
dc.description.affiliationRoyal Brisbane & Womens Hosp, Brisbane, Qld 4029, Australia
dc.description.affiliationUnifespUniversidade Federal de São Paulo, EPM, Dept Anat Patol, BR-04024000 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipLudwig Institute of Cancer Research
dc.description.sponsorshipNational Breast Cancer Foundation
dc.format.extent13
dc.identifierhttp://dx.doi.org/10.1186/bcr2603
dc.identifier.citationBreast Cancer Research. London: Biomed Central Ltd, v. 12, n. 4, 13 p., 2010.
dc.identifier.doi10.1186/bcr2603
dc.identifier.fileWOS000285504100002.pdf
dc.identifier.issn1465-542X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32046
dc.identifier.wosWOS:000285504100002
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofBreast Cancer Research
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleHER3 and downstream pathways are involved in colonization of brain metastases from breast canceren
dc.typeinfo:eu-repo/semantics/article
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