Expression of human papillomavirus type 16 E6-E7 open reading frame varies quantitatively in biopsy tissue from different grades of cervical intraepithelial neoplasia.
The proteins encoded by the human papillomavirus type 16 E6-E7 open reading frame are essential for transformation of the host cell. Two mRNA species, E6*I and E6*II, generated by alternative splicing of a polycistronic pre-mRNA, encode truncated E6 proteins and the E7 protein. Our investigation assessed whether or not the level of expression of E6*I and E6*II varies quantitatively in relation to the grade of cervical intraepithelial neoplasia (CIN). We used a quantitative reverse transcription PCR assay to quantify these transcripts in concurrently collected biopsy tissue and exfoliated cervical cells from 22 women with a normal cervix or various grades of CIN. We evaluated transcription profiles in relation to CIN grade and specimen type. The expression levels of E6*I and E6*II in exfoliated cervical cells did not vary significantly in relation to the grade of CIN. However, expression of E6*II was significantly diminished or absent in biopsy tissue obtained from CIN grade II and III lesions (P = 0.014). Our findings suggest that quantification of E6*I and E6*II expression in biopsy tissue may be more clinically relevant than analysis of exfoliated cells. The identification of distinct patterns of expression in association with low- and high-grade CIN suggests that quantification of E6*I and E6*II expression in biopsy tissue may have prognostic value as an indicator of CIN progression.
McNicol
P
P
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
Guijon
F
F
Wayne
S
S
Hidajat
R
R
Paraskevas
M
M
D001483:Base Sequence; D002278:Carcinoma in Situ / Q000821:virology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D016366:Open Reading Frames; D027383:Papillomaviridae / Q000235:genetics* / Q000472:pathogenicity; D050725:Papillomavirus E7 Proteins; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012097:Repressor Proteins; D002583:Uterine Cervical Neoplasms / Q000821:virology*
D017931:DNA Primers; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16