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Article: Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours

TitleExpression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours
Authors
Issue Date2002
PublisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130
Citation
Journal Of Pathology, 2002, v. 196 n. 2, p. 145-153 How to Cite?
AbstractFrizzled-related protein (Frp) is a new family of secreted proteins that contain a region homologous to the extracellular cysteine-rich domain (CRD) of the frizzled family proteins. The role of Frp protein is far from clear. To explore the role of Frp and its relationship to the Wnt-signalling pathway in breast cancer, in situ hybridization and immunohistochemical analyses of Frp, Wnt-1, APC, β-catenin, and its target genes c-myc and cyclin D1 were conducted in 70 specimens of invasive ductal carcinomas of the human breast. Frp mRNA was down-regulated in 62 and elevated in eight tumour specimens, compared with adjacent normal tissues. In the course of tumour progression, however, Frp mRNA steadily increased in both tumour and the adjacent tissues. Interestingly, the number of cases with axillary lymph node metastasis was significantly lower in the group with elevated Frp than in the group with decreased Frp, suggesting that Frp may contribute as a prognostic factor in invasive breast cancer. Wnt-1, a gene implicated in human breast cancer, was markedly elevated in grade 1 tumours, but declined as tumour grade declined. The level of Wnt-1 was linearly correlated with its downstream target β-catenin (p < 0.05), but was inversely correlated with Frp (p < 0.05), suggesting a possible negative regulatory role of Frp with regard to Wnt-1. APC was inversely correlated with β-catenin (p < 0.05). β-catenin, a key transcriptional activator responsible for the activation of both c-myc and cyclin D1 in colorectal tumours, was detected at high levels in the plasma membranes of cells in normal tissue. In tumour masses, however, β-catenin lost its tight association with the membrane and diffused into the cytoplasm. Surprisingly, it clearly did not penetrate the nuclei, despite the fact that both c-myc and cyclin D1 were markedly elevated in all tumour tissues. As revealed in this study, Wnt-1/β-catenin plays very different roles in the oncogenesis of breast and colon cancers. This first systemic analysis of the Frp and the Wnt-signalling pathway in human breast cancer provides a springboard for further work on the role of Frp in the development of breast cancer. Copyright © 2001 John Wiley & Sons, Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/88715
ISSN
2015 Impact Factor: 7.381
2015 SCImago Journal Rankings: 4.176
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, SCCen_HK
dc.contributor.authorLo, SFEen_HK
dc.contributor.authorLee, KCen_HK
dc.contributor.authorYam, JWPen_HK
dc.contributor.authorChan, JKCen_HK
dc.contributor.authorWendy Hsiao, WLen_HK
dc.date.accessioned2010-09-06T09:47:01Z-
dc.date.available2010-09-06T09:47:01Z-
dc.date.issued2002en_HK
dc.identifier.citationJournal Of Pathology, 2002, v. 196 n. 2, p. 145-153en_HK
dc.identifier.issn0022-3417en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88715-
dc.description.abstractFrizzled-related protein (Frp) is a new family of secreted proteins that contain a region homologous to the extracellular cysteine-rich domain (CRD) of the frizzled family proteins. The role of Frp protein is far from clear. To explore the role of Frp and its relationship to the Wnt-signalling pathway in breast cancer, in situ hybridization and immunohistochemical analyses of Frp, Wnt-1, APC, β-catenin, and its target genes c-myc and cyclin D1 were conducted in 70 specimens of invasive ductal carcinomas of the human breast. Frp mRNA was down-regulated in 62 and elevated in eight tumour specimens, compared with adjacent normal tissues. In the course of tumour progression, however, Frp mRNA steadily increased in both tumour and the adjacent tissues. Interestingly, the number of cases with axillary lymph node metastasis was significantly lower in the group with elevated Frp than in the group with decreased Frp, suggesting that Frp may contribute as a prognostic factor in invasive breast cancer. Wnt-1, a gene implicated in human breast cancer, was markedly elevated in grade 1 tumours, but declined as tumour grade declined. The level of Wnt-1 was linearly correlated with its downstream target β-catenin (p < 0.05), but was inversely correlated with Frp (p < 0.05), suggesting a possible negative regulatory role of Frp with regard to Wnt-1. APC was inversely correlated with β-catenin (p < 0.05). β-catenin, a key transcriptional activator responsible for the activation of both c-myc and cyclin D1 in colorectal tumours, was detected at high levels in the plasma membranes of cells in normal tissue. In tumour masses, however, β-catenin lost its tight association with the membrane and diffused into the cytoplasm. Surprisingly, it clearly did not penetrate the nuclei, despite the fact that both c-myc and cyclin D1 were markedly elevated in all tumour tissues. As revealed in this study, Wnt-1/β-catenin plays very different roles in the oncogenesis of breast and colon cancers. This first systemic analysis of the Frp and the Wnt-signalling pathway in human breast cancer provides a springboard for further work on the role of Frp in the development of breast cancer. Copyright © 2001 John Wiley & Sons, Ltd.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130en_HK
dc.relation.ispartofJournal of Pathologyen_HK
dc.rightsJournal of Pathology. Copyright © John Wiley & Sons Ltd.en_HK
dc.subject.meshAdenomatous Polyposis Coli Protein - analysisen_HK
dc.subject.meshBreast - chemistryen_HK
dc.subject.meshBreast Neoplasms - chemistry - pathologyen_HK
dc.subject.meshCarcinoma, Ductal, Breast - chemistry - pathologyen_HK
dc.subject.meshCell Membrane - chemistryen_HK
dc.subject.meshCyclin D1 - analysisen_HK
dc.subject.meshCytoskeletal Proteins - analysisen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshFollistatin-Related Proteinsen_HK
dc.subject.meshGlycoproteins - analysis - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshIn Situ Hybridizationen_HK
dc.subject.meshProto-Oncogene Proteins - analysis - metabolismen_HK
dc.subject.meshProto-Oncogene Proteins c-myc - analysisen_HK
dc.subject.meshSignal Transductionen_HK
dc.subject.meshTrans-Activatorsen_HK
dc.subject.meshWnt Proteinsen_HK
dc.subject.meshWnt1 Proteinen_HK
dc.subject.meshZebrafish Proteinsen_HK
dc.subject.meshbeta Cateninen_HK
dc.titleExpression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumoursen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3417&volume=196&spage=145&epage=153&date=2002&atitle=Expression+of+frizzled-related+protein+and+Wnt-signalling+molecules+in+invasive+human+breast+tumoursen_HK
dc.identifier.emailYam, JWP:judyyam@pathology.hku.hken_HK
dc.identifier.authorityYam, JWP=rp00468en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/path.1035en_HK
dc.identifier.pmid11793365-
dc.identifier.scopuseid_2-s2.0-0036154038en_HK
dc.identifier.hkuros66028en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036154038&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume196en_HK
dc.identifier.issue2en_HK
dc.identifier.spage145en_HK
dc.identifier.epage153en_HK
dc.identifier.isiWOS:000173593500003-
dc.publisher.placeUnited Kingdomen_HK

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