All-trans retinoic acid (ATRA) suppresses transcription of human papillomavirus type 16 (HPV16) in a dose-dependent manner.
Earlier we found that SiHa cervical squamous carcinoma cells that harbor HPV type 16 respond to ATRA treatment in a dose-dependent manner: high-dose (10(-5)-10(-4) M) but not low-dose (10(-7)-10(-6) M) ATRA induced growth arrest. Growth of HPV-infected cells is highly dependent on the expression of the viral E6/E7 proteins. Thus, targeting expression of the viral E6/E7 genes might influence growth properties of HPV-infected cells. Here, we demonstrated that high-dose ATRA inhibited expression of HPV16 E7 through suppression of the HPV16 promoter (p97) activity. Gelshift assay (EMSA) revealed that binding of the AP-1 transcription factor to an oligonucleotide originated from the HPV type 16 promoter was diminished after high-dose, but not low-dose ATRA treatment. This suggests that high-dose ATRA suppresses HPV 16 promoter activity, at least in part, via a decreased AP-1 binding. Our data might be useful in treatment of cervical dysplasias and/or carcinomas.
Faluhelyi
Zsolt
Z
Department of Oncology, Baranya County Hospital, Pécs, Hungary.
Rodler
Imre
I
Csejtey
Andras
A
Tyring
Stephen K
SK
Ember
Istvan A
IA
Arany
Istvan
I
D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000821:virology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D027383:Papillomaviridae / Q000187:drug effects* / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000821:virology
D000970:Antineoplastic Agents; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D014212:Tretinoin