The link between integration and expression of human papillomavirus type 16 genomes and cellular changes in the evolution of cervical intraepithelial neoplastic lesions.
We have matched a PCR assay which detects disruptions in the E2 reading frame of human papillomavirus type 16, with RNA in situ hybridization patterns and shown that in 15 out of 16 cervical intraepithelial neoplastic (CIN) III lesions and in 19 out of 19 tumours, the E2 gene is disrupted with no detectable E2 transcripts. Varying levels of E6-E7 transcripts are detected in CIN III lesions, with stronger signals in tumours. The cytokeratin profile of most tumours: cytokeratin 10-, 14- and 19-positive and 4-, 13- and 18-negative, is also detected in CIN III lesions. The changes in levels of alpha 2, beta 1 and beta 4 integrins, CD44 and E-cadherin occur during the evolution of high-grade CIN lesions. Increases in the levels of expression of CD44 and E6-E7 transcripts, coupled with changes in the cellular localization of the Notch protein, define the transition from CIN III lesions to tumours.
Daniel
B
B
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India. betty@ncbs.tifrbng.res.in
Rangarajan
A
A
Mukherjee
G
G
Vallikad
E
E
Krishna
S
S
D015820:Cadherins / Q000378:metabolism; D004268:DNA-Binding Proteins; D015870:Gene Expression; D016679:Genome, Viral; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016662:Virus Integration; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology / Q000821:virology*
D015820:Cadherins; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C068651:E6 protein, Human papillomavirus type 16; D018960:Hyaluronan Receptors; D016023:Integrins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007633:Keratins