[en] Amongst high-risk human papillomaviruses (HPV), HPV-16 infection is the most
prevalent causative factor for cervical cancer. Beside other mucosal targets, HPV-16
was reported to infect the placenta and to replicate in trophoblastic cells. Since these
cells share invasive properties of tumoral cells, they represent an ideal model to
investigate several oncogenic processes. In the present work, we analyzed the impacts
of HPV-16 E5, E6 and E7 oncoproteins on the trophoblastic model. Our results
showed that E5 impaired the viability of trophoblastic and cervical cell lines but E6
and E7, favouring cell growth, neutralised the E5 cytotoxic effect. In addition, E5
decreased the adhesiveness of trophoblastic cells to the tissue culture plastic and to
endometrial cells similarly as previously described for E6 and E7. E5 and E6 plus E7
increased also their migration and their invasive properties. Cells expressing HPV-16
early proteins under the control of the LCR endogenous promoter displayed growth
advantage and were also more motile and invasive compared to control cells.
Interestingly, the E-cadherin was down regulated in trophoblastic cells expressing E5,
E6 and E7. NF-kB and AP-1 activities were also enhanced. In conclusion, HPV-16
early proteins enhanced trophoblastic growth and intensify the malignant phenotype
by impairing cell adhesion leading to increased cellular motile and invasive
properties. HPV-16 E5 participated, with E6 and E7, in these changes by impairing Ecadherin
expression, a hallmark of malignant progression.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Boulenouar, S.
Weyn, C.
Van Noppen, M.
Moussa Ali, M.
Favre, M.
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Bex, F.
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Englert, Y.
Fontaine, V.
Language :
English
Title :
Effects of HPV-16 E5, E6 and E7 Proteins on Survival, Adhesion, Migration and Invasion of Trophoblastic Cells
Publication date :
2010
Journal title :
Carcinogenesis
ISSN :
0143-3334
eISSN :
1460-2180
Publisher :
Irl Press at Oxford University Press, Oxford, United Kingdom
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