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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Disc large 1 expression is altered by human papillomavirus E6/E7 proteins in organotypic cultures of human keratinocytes

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Bugnon Valdano, M. [1] ; Cavatorta, A. L. [1] ; Morale, M. G. [2] ; Marziali, F. [1] ; de Souza Lino, V. [3] ; Steenbergen, R. D. M. [4] ; Boccardo, E. [3] ; Gardiol, D. [1]
Total Authors: 8
[1] Univ Nacl Rosario, Inst Biol Mol & Celular Rosario, CONICET, Fac Ciencias Bioquim & Farmaceut, Suipacha 531, RA-2000 Rosario, Santa Fe - Argentina
[2] Univ Sao Paulo, Dept Biochem, Inst Chem, Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil
[4] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam - Netherlands
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF GENERAL VIROLOGY; v. 97, n. 2, p. 453-462, FEB 2016.
Web of Science Citations: 3

Loss of cell polarity is a fundamental process in cell transformation. Among polarity proteins, we focused on human disc large (DLG1), which is localized mainly at adherens junctions and contributes to the control of cell proliferation. We previously demonstrated that its expression is altered in HPV-associated cervical neoplastic lesions, but the mechanisms beyond this remain unknown. In this study, we analysed the contribution of HPV proteins to the changes in DLG1 expression in the squamous epithelium. We observed tissue and intracellular misdistribution of DLG1 when high-risk HPV-18 E7 or E6/E7 proteins were expressed in organotypic raft cultures. The viral oncoproteins induce the loss of DLG1 from the cell borders and an increase in the level of DLG1 protein, reflecting the pattern observed in cervical lesions. These findings were corroborated in cultures bearing the entire HPV-18 genome. Interestingly, changes in tissue distribution and abundance of DLG1 were also detected in organotypic cultures expressing the low-risk HPV-11 E7 or E6/E7 proteins, suggesting a conserved function among different HPV types. However, for low-risk HPVs, the subcellular localization of DLG1 at cell-to-cell contacts was predominantly maintained. This report offers new evidence, we believe, of the involvement of HPV proteins in DLG1 expression pattern and our data support previous observations regarding DLG1 expression in cervical lesions. (AU)

FAPESP's process: 12/51017-8 - Analysis of polarity proteins expression in neoplastic processes associated with human Papillomavirus using organotypic cultures.
Grantee:Enrique Mario Boccardo Pierulivo
Support Opportunities: Regular Research Grants