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dc.contributor.authorStankiewicz, Elzbieta
dc.contributor.authorProwse, David M.
dc.contributor.authorNg, Mansum
dc.contributor.authorCuzick, Jack
dc.contributor.authorMesher, David
dc.contributor.authorHiscock, Frances
dc.contributor.authorLu, Yong Jie
dc.contributor.authorWatkin, Nicholas
dc.contributor.authorCorbishley, Catherine
dc.contributor.authorLam, Wayne
dc.contributor.authorBerney, Daniel M.
dc.date.accessioned2015-06-30T07:20:58Z
dc.date.available2015-06-30T07:20:58Z
dc.date.issued2011-03-10
dc.identifier.citationStankiewicz , E , Prowse , D M , Ng , M , Cuzick , J , Mesher , D , Hiscock , F , Lu , Y J , Watkin , N , Corbishley , C , Lam , W & Berney , D M 2011 , ' Alternative HER/PTEN/Akt pathway activation in HPV positive and negative penile carcinomas ' , PLoS ONE , vol. 6 , no. 3 , e17517 . https://doi.org/10.1371/journal.pone.0017517
dc.identifier.issn1932-6203
dc.identifier.otherPURE: 8682599
dc.identifier.otherPURE UUID: 4f7f91a8-e2cb-4ec9-980f-817c4fa40960
dc.identifier.otherScopus: 79952284289
dc.identifier.otherPubMed: 21407808
dc.identifier.urihttp://hdl.handle.net/2299/16100
dc.descriptionCopyright: 2011 Stankiewicz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.description.abstractBackground: The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood, though risk factors include human papillomavirus (HPV). Disruption of HER/PTEN/Akt pathway is present in many cancers; however there is little information on its function in PSCC. We investigated HER family receptors and phosphatase and tension homolog (PTEN) in HPV-positive and negative PSCC and its impact on Akt activation using immunohistochemistry and fluorescent in situ hybridisation (FISH). Methodology/Principal Findings: 148 PSCCs were microarrayed and immunostained for phosphorylated EGFR (pEGFR), HER2, HER3, HER4, phosphorylated Akt (pAkt), Akt1 and PTEN proteins. EGFR and PTEN gene status were also evaluated using FISH. HPV presence was assessed by PCR. pEGFR expression was detected significantly less frequently in HPV-positive than HPV-negative tumours (p = 0.0143). Conversely, HER3 expression was significantly more common in HPV-positive cases (p = 0.0128). HER4, pAkt, Akt and PTEN protein expression were not related to HPV. HER3 (p = 0.0054) and HER4 (p = 0.0002) receptors significantly correlated with cytoplasmic Akt1 immunostaining. All three proteins positively correlated with tumour grade (HER3, p = 0.0029; HER4, p = 0.0118; Akt1, p = 0.0001). pEGFR expression correlated with pAkt but not with tumour grade or stage. There was no EGFR gene amplification. HER2 was not detected. PTEN protein expression was reduced or absent in 62% of tumours but PTEN gene copy loss was present only in 4% of PSCCs. Conclusions/Significance: EGFR, HER3 and HER4 but not HER2 are associated with penile carcinogenesis. HPV-negative tumours tend to express significantly more pEGFR than HPV-positive cancers and this expression correlates with pAkt protein, indicating EGFR as an upstream regulator of Akt signalling in PSCC. Conversely, HER3 expression is significantly more common in HPV-positive cases and positively correlates with cytoplasmic Akt1 expression. HER4 and PTEN protein expression are not related to HPV infection. Our results suggest that PSCC patients could benefit from therapies developed to target HER receptors.en
dc.language.isoeng
dc.relation.ispartofPLoS ONE
dc.subjectAgricultural and Biological Sciences(all)
dc.subjectBiochemistry, Genetics and Molecular Biology(all)
dc.subjectMedicine(all)
dc.titleAlternative HER/PTEN/Akt pathway activation in HPV positive and negative penile carcinomasen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionBiosciences Research Group
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=79952284289&partnerID=8YFLogxK
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1371/journal.pone.0017517
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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