Silencing of E7 oncogene restores functional E-cadherin expression in human papillomavirus 16-transformed keratinocytes.
Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The persistence or progression of cervical lesions suggests that viral antigens are not adequately presented to the immune system. This hypothesis is reinforced by the observation that most squamous intra-epithelial lesions show quantitative and functional alterations of Langerhans cells (LCs). Moreover, E-cadherin-dependent adhesion of LC to keratinocytes (KCs) is defective in cervical HPV16-associated (pre)neoplastic lesions. The possible role of viral oncoprotein E7 in the reduced levels of cell surface E-cadherin was investigated by silencing HPV16 E7 by RNA interference (siRNA). This treatment induced an increased cell surface E-cadherin expression in HPV16-positive KC and a significant adhesion of LC to these squamous cells. The E-cadherin re-expression following HPV16 E7 silencing was associated with increased detection levels of retinoblastoma protein and the activating protein (AP)-2alpha transcription factor. These data suggest that HPV16 E7-induced alterations of LC/KC adhesion may play a role in the defective immune response during cervical carcinogenesis.
Department of Pathology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer, B23, University of Liege, Centre Hospitalier Universitaire Sart Tilman, 4000 Liege, Belgium. jhcaberg@student.ulg.ac.be
Jean-Hubert D
JH
Caberg
Pascale M
PM
Hubert
Dominique Y
DY
Begon
Michael F
MF
Herfs
Patrick J
PJ
Roncarati
Jacques J
JJ
Boniver
Philippe O
PO
Delvenne
D018949:Antigens, CD1 / Q000096:biosynthesis; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000235:genetics* / Q000276:immunology; D005260:Female; D020868:Gene Silencing; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D050656:Transcription Factor AP-2 / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*
D018949:Antigens, CD1; C419393:CD1a antigen; D015820:Cadherins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050656:Transcription Factor AP-2; C059731:oncogene protein E7, Human papillomavirus type 16