HPV16 Oncoproteins Induce MMPs/RECK-TIMP-2 Imbalance in Primary Keratinocytes: Possible Implications in Cervical Carcinogenesis

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCARDEAL, Laura Beatriz da Silva
dc.contributor.authorBOCCARDO, Enrique
dc.contributor.authorTERMINI, Lara
dc.contributor.authorRABACHINI, Tatiana
dc.contributor.authorANDREOLI, Maria Antonieta
dc.contributor.authorLORETO, Celso di
dc.contributor.authorLONGATTO FILHO, Adhemar
dc.contributor.authorVILLA, Luisa Lina
dc.contributor.authorMARIA-ENGLER, Silvya Stuchi
dc.date.accessioned2013-07-30T17:53:44Z
dc.date.available2013-07-30T17:53:44Z
dc.date.issued2012
dc.description.abstractCervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/ RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome.
dc.description.indexMEDLINE
dc.description.sponsorshipFAPESP Sao Paulo Research Foundation [2005/58885-1, 2008/58817-4, 2008/03232-1]
dc.description.sponsorshipPRPG-USP: Pro-Reitoria de Pos-Graduacao da Universidade de Sao Paulo
dc.description.sponsorshipCNPq: Conselho Nacional de Pesquisa e Desenvolvimento
dc.identifier.citationPLOS ONE, v.7, n.3, article ID e33585, 9p, 2012
dc.identifier.doi10.1371/journal.pone.0033585
dc.identifier.issn1932-6203
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/1606
dc.language.isoeng
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relation.ispartofPlos One
dc.rightsopenAccess
dc.rights.holderCopyright PUBLIC LIBRARY SCIENCE
dc.subject.othercysteine-rich protein
dc.subject.othermatrix-metalloproteinase
dc.subject.othertumor microenvironment
dc.subject.otherclinical-significance
dc.subject.othercancer progression
dc.subject.othertissue inhibitor
dc.subject.othergene-expression
dc.subject.othercarcinoma cells
dc.subject.otherregulator reck
dc.subject.otheruterine cervix
dc.subject.wosMultidisciplinary Sciences
dc.titleHPV16 Oncoproteins Induce MMPs/RECK-TIMP-2 Imbalance in Primary Keratinocytes: Possible Implications in Cervical Carcinogenesis
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalCARDEAL, Laura Beatriz da Silva:Univ Sao Paulo, Sch Pharmaceut Sci, Clin Chem & Toxicol Dept, Sao Paulo, Brazil
hcfmusp.author.externalBOCCARDO, Enrique:Ludwig Inst Canc Res, Virol Grp, Sao Paulo, Brazil; Univ Sao Paulo, Dept Microbiol, Inst Biomed Sci, Sao Paulo, Brazil
hcfmusp.author.externalTERMINI, Lara:Ludwig Inst Canc Res, Virol Grp, Sao Paulo, Brazil; HPV Inst INCT HPV, Sao Paulo, Brazil
hcfmusp.author.externalRABACHINI, Tatiana:Ludwig Inst Canc Res, Virol Grp, Sao Paulo, Brazil
hcfmusp.author.externalANDREOLI, Maria Antonieta:Ludwig Inst Canc Res, Virol Grp, Sao Paulo, Brazil
hcfmusp.author.externalLORETO, Celso di:Nucleo Patol Inst Adolfo Lutz, Sao Paulo, Brazil
hcfmusp.author.externalVILLA, Luisa Lina:Ludwig Inst Canc Res, Virol Grp, Sao Paulo, Brazil; HPV Inst INCT HPV, Sao Paulo, Brazil
hcfmusp.author.externalMARIA-ENGLER, Silvya Stuchi:Univ Sao Paulo, Sch Pharmaceut Sci, Clin Chem & Toxicol Dept, Sao Paulo, Brazil
hcfmusp.citation.scopus52
hcfmusp.contributor.author-fmusphcADHEMAR LONGATTO FILHO
hcfmusp.description.articlenumbere33585
hcfmusp.description.issue3
hcfmusp.description.volume7
hcfmusp.lim.ref2012
hcfmusp.origemWOS
hcfmusp.origem.pubmed22438955
hcfmusp.origem.scopus2-s2.0-84858378580
hcfmusp.origem.wosWOS:000303309100063
hcfmusp.publisher.citySAN FRANCISCO
hcfmusp.publisher.countryUSA
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hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
hcfmusp.remissive.sponsorshipUSP
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