Please use this identifier to cite or link to this item: http://buratest.brunel.ac.uk/handle/2438/5678
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dc.contributor.authorPatani, N-
dc.contributor.authorJiang, W-
dc.contributor.authorNewbold, R-
dc.contributor.authorMokbel, K-
dc.date.accessioned2011-07-29T09:19:57Z-
dc.date.available2011-07-29T09:19:57Z-
dc.date.issued2010-
dc.identifier.citationJournal of Carcinogenesis, 9(Online Paper): 9, Nov 2010en_US
dc.identifier.issn1477-3163-
dc.identifier.urihttp://bura.brunel.ac.uk/handle/2438/5678-
dc.descriptionThis article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2010 Patani.en_US
dc.description.abstractBackground: Ubiquitin modification of proteins influences cellular processes relevant to carcinogenesis. CHIP (carboxyl-terminus of Hsc70-interacting protein) is a chaperone-dependent E3 ubiquitin ligase, regulating the stability of heat shock protein 90 (HSP90) interacting proteins. CHIP is implicated in the modulation of estrogen receptor (ESR1) and Her-2/neu (ERBB2) stability. LOX (lysyl-oxidase) serves intracellular roles and catalyses the cross-linking of extracellular matrix (ECM) collagens and elastin. LOX expression is altered in human malignancies and their peri-tumoral stroma. However, paradoxical roles are reported. In this study, the level of mRNA expression of CHIP and LOX were assessed in normal and malignant breast tissue and correlated with clinico-pathological parameters. Materials and Methods: Breast cancer (BC) tissues (n = 127) and normal tissues (n = 33) underwent RNA extraction and reverse transcription; transcript levels were determined using real-time quantitative PCR and normalized against CK-19. Transcript levels were analyzed against TNM stage, nodal involvement, tumor grade and clinical outcome over a ten-year follow-up period. Results: CHIP expression decreased with increasing Nottingham Prognostic Index (NPI): NPI-1 vs. NPI-3 (12.2 vs. 0.2, P = 0.0264), NPI-2 vs. NPI-3 (3 vs. 0.2, P = 0.0275). CHIP expression decreased with increasing TNM stage: TNM-1 vs. TNM-2 (12 vs. 0, P = 0.0639), TNM-1 vs. TNM-2-4 (12 vs. 0, P = 0.0434). Lower transcript levels were associated with increasing tumor grade: grade 1 vs. grade 3 (17.7 vs. 0.3, P = 0.0266), grade 2 vs. grade 3 (5 vs. 0.3, P = 0.0454). The overall survival (OS) for tumors classified as ‘low-level expression’, was poorer than those with ‘high-level expression’ (118.1 vs. 152.3 months, P = 0.039). LOX expression decreased with increasing NPI: NPI-1 vs. NPI-2 (3 vs. 0, P = 0.0301) and TNM stage: TNM-1 = 3854639, TNM-2 = 908900, TNM-3 = 329, TNM-4 = 1.232 (P = NS). Conclusion: CHIP expression is associated with favorable prognostic parameters, including tumor grade, TNM stage and NPI. CHIP expression predicts OS. LOX expression is associated with improved NPI. In addition to their prognostic utility, mechanistic insights into tumor suppressor function may offer potential therapeutic strategies.en_US
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.subjectBreast canceren_US
dc.subjectPrognosisen_US
dc.subjectRecurrenceen_US
dc.subjectSurvivalen_US
dc.subjectTumor suppressoren_US
dc.titlePrognostic implications of carboxyl-terminus of Hsc70 interacting protein and lysyl-oxidase expression in human breast canceren_US
dc.typeResearch Paperen_US
dc.identifier.doihttp://dx.doi.org/10.4103/1477-3163.72505-
pubs.organisational-data/Brunel-
pubs.organisational-data/Brunel/Brunel (Active)-
pubs.organisational-data/Brunel/Brunel (Active)/School of Health Science & Social Care-
pubs.organisational-data/Brunel/Research Centres-
pubs.organisational-data/Brunel/Research Centres/BICGP-
pubs.organisational-data/Brunel/School of Health Sciences and Social Care-
pubs.organisational-data/Brunel/School of Health Sciences and Social Care/BICGP-
Appears in Collections:Biological Sciences
Cancer
Dept of Life Sciences Research Papers

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