title: Sequence variation in the E2-binding domain of HPV16 and biological function evaluation in Tunisian cervical cancers.
abstract: HPV16 E2 variants have different effects on the transcriptional activity of the LCR. In this study, we examined the nucleotide and amino acid sequence variation within the HPV16 E2 gene and to correlate with disease progression. E2 gene disruption was detected by PCR amplification of the entire E2 gene using a single set of primers. Nucleotide variations were analyzed by bidirectional sequencing. mRNA expression patterns of E6 and E7 gene transcripts were evaluated by a reverse transcriptase-PCR method (RT-PCR). The detection of intact E2 genes was significantly higher among controls than cases (81.8% versus 37.5%, resp., P < 0.05). Among the E subgroup, variation at position 3684 C>A results in the amino acid substitution T310K and was more common among the E2 undisrupted cases (7/9; 77.7%), compared to controls (2/9; 22.2%). In addition, specific sequence variations identified in the E2 ORF at positions 3684 C>A were associated with increased viral oncogenes E6-E7 production. Besides HPV16 E2 disruption, the 3684 C>A variation within undisrupted E2 genes could be involved in an alternative mechanism for deregulating the expression of the HPV16 E6 and E7 oncogenes and appears to be a major factor contributing to the development of cervical cancer in Tunisian women.
authors.affiliation: Unit of Immuno-Microbio-Environmental and Carcinogenesis (IMEC), Faculty of Sciences, University of Carthage, Jarzouna, 7021 Bizerta, Tunisia.
authors.forename: Saloua
authors.initials: S
authors.lastname: Kahla
authors.affiliation: Radio-oncology Department, Salah Azaiz Institute, 1006 Tunis, Tunisia.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Kochbati
authors.affiliation: Research Laboratory of Antimicrobial Resistance, Faculty of Medicine of Tunis, 1007 Tunis, Tunisia.
authors.forename: Samia
authors.initials: S
authors.lastname: Hammami
authors.affiliation: Service of Gynaecology Obstetrics A, Center of Maternity and Neonatology, Hospital La Rabta, 1007 Tunis, Tunisia.
authors.forename: Mohamed Badis
authors.initials: MB
authors.lastname: Chanoufi
authors.affiliation: Radio-oncology Department, Salah Azaiz Institute, 1006 Tunis, Tunisia.
authors.forename: Mongi
authors.initials: M
authors.lastname: Maalej
authors.affiliation: Unit of Immuno-Microbio-Environmental and Carcinogenesis (IMEC), Faculty of Sciences, University of Carthage, Jarzouna, 7021 Bizerta, Tunisia.
authors.forename: Ridha
authors.initials: R
authors.lastname: Oueslati
mesh_terms: D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics*; D014416:Tunisia; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16