E7 properties of mucosal human papillomavirus types 26, 53 and 66 correlate with their intermediate risk for cervical cancer development.
Epidemiological studies have demonstrated that 15 different mucosal human papillomavirus (HPV) types of the genus alpha of the HPV phylogetic tree are classified as high risk for cervical cancer development. Three additional HPV types of the same genus, HPV26, 53 and 66, are classified as probable high-risk types. In this study, we have characterized the biological properties of the E7 oncoproteins from these three HPV types. All of the corresponding E7 proteins were able to associate with retinoblastoma protein (pRb) and up-regulated the expression of several positive cell cycle regulators, i.e. CDK2, cyclin A and cylin E. However, HPV26 E7 appears to be more efficient than HPV53 and 66 E7 in up-regulating the transcription of cyclin A. Unlike E7 from the high-risk type HPV16 protein, HPV26, 53 and 66 did not efficiently promote pRb degradation. In addition, E7 from these viruses was able to promote proliferation of primary human keratinocytes and circumvent G1 arrest imposed by overexpression of p16(INK4a), but with less efficiency than the high-risk HPV16 E7. Together, our data show that in vitro properties of these E7 proteins correlate with the epidemiological classification of HPV26, 53 and 66 as HPV types with an intermediate risk for cervical cancer development.
Mansour
Mariam
M
Infections and Cancer Biology Group, International Agency for Research on Cancer, 150 cours Albert-Thomas, 69008 Lyon, France.
Touka
Majid
M
Hasan
Uzma
U
Bellopede
Angelica
A
Smet
Anouk
A
Accardi
Rosita
R
Gabet
Anne-Sophie
AS
Sylla
Bakary S
BS
Tommasino
Massimo
M
D052685:Alphapapillomavirus / Q000145:classification* / Q000378:metabolism / Q000472:pathogenicity*; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D019925:Cyclin A / Q000187:drug effects / Q000378:metabolism; D019927:Cyclin E / Q000187:drug effects / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D030361:Papillomavirus Infections / Q000821:virology; D016160:Retinoblastoma Protein / Q000378:metabolism; D012307:Risk Factors; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000821:virology
D019925:Cyclin A; D019927:Cyclin E; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2