Carcinogenesis, Vol 19, 1481-1486, Copyright © 1998 by Oxford University Press
XF Pei, L Sherman, YH Sun and R Schlegel
The E6 and E7 genes of HPV-16 or HPV-18 both are necessary for effective
immortalization of primary human genital keratinocytes. To analyse the
individual role of E6 and E7 genes in dysregulating cell growth, we cloned
the HPV-16 E6, E7 and E6/E7 genes into retroviruses. Primary human
keratinocytes (PHK) were then infected with these retroviruses and selected
in differentiation-inducing medium (high calcium and serum). The E6/E7
retroviruses were the most effective at inducing differentiation-resistant
colonies. Intermediate numbers of colonies were induced by E6 and low
numbers by E7. Interestingly, only cultures infected with E7 and E6/E7
retroviruses showed a significant proportion of cells progressing into the
S phase, consistent with our earlier studies showing that E7 is required
for the efficient immortalization of genital keratinocytes. Accompanying
this entry into S phase, the E7 or E6/E7 transduced cells expressed high
levels of cyclins A, B and E, but lower levels of cyclin D. In addition,
cdc-2, cdk-2 and cdk-4 were also increased. No significant differences were
detected in the expression of c-myc and c-fos between the vector and any of
the transduced cells. Keratinocytes infected with the E7 retrovirus
exhibited decreased levels of Rb protein and increased levels of p53,
whereas cells infected with E6-expressing retroviruses displayed normal
levels of Rb protein and decreased levels of p53. Finally, E7 induced a
three-fold increase in bcl-2 expression. Our results indicate that the
HPV-16 E7 gene alone is sufficient to bypass keratinoctye growth arrest
induced by serum and calcium exposure and that the discordant expression of
several cell regulatory proteins accompanies this unregulated
proliferation.
ARTICLES
HPV-16 E7 protein bypasses keratinocyte growth inhibition by serum and calcium
Department of Pathology, Georgetown University Medical School, Washington, DC 20007, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C.-H. Lin, H.-S. Chang, and W. C. Y. Yu USP11 Stabilizes HPV-16E7 and Further Modulates the E7 Biological Activity J. Biol. Chem., June 6, 2008; 283(23): 15681 - 15688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. E. Ferguson and D. H. Oh Proficient Global Nucleotide Excision Repair in Human Keratinocytes but not in Fibroblasts Deficient in p53 Cancer Res., October 1, 2005; 65(19): 8723 - 8729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. McMurray and D. J. McCance Degradation of p53, Not Telomerase Activation, by E6 Is Required for Bypass of Crisis and Immortalization by Human Papillomavirus Type 16 E6/E7 J. Virol., June 1, 2004; 78(11): 5698 - 5706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. He, D. Staples, C. Smith, and C. Fisher Direct Activation of Cyclin-Dependent Kinase 2 by Human Papillomavirus E7 J. Virol., October 1, 2003; 77(19): 10566 - 10574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Du, G. G. Chen, A. C. Vlantis, H. Xu, R. K.Y. Tsang, and A. C. van Hasselt The Nuclear Localization of NF{kappa}B and p53 Is Positively Correlated with HPV16 E7 Level in Laryngeal Squamous Cell Carcinoma J. Histochem. Cytochem., April 1, 2003; 51(4): 533 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. DeFilippis, E. C. Goodwin, L. Wu, and D. DiMaio Endogenous Human Papillomavirus E6 and E7 Proteins Differentially Regulate Proliferation, Senescence, and Apoptosis in HeLa Cervical Carcinoma Cells J. Virol., December 20, 2002; 77(2): 1551 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Lee, B.-C. Kim, I. Y. Kim, E.-a. Cho, D. J. Satterwhite, and S.-J. Kim The Human Papilloma Virus E7 Oncoprotein Inhibits Transforming Growth Factor-beta Signaling by Blocking Binding of the Smad Complex to Its Target Sequence J. Biol. Chem., October 4, 2002; 277(41): 38557 - 38564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Berger, A. Baege, T. Guillemette, J. Deeds, R. Meyer, G. Disbrow, R. Schlegel, and R. Schlegel Insulin-Like Growth Factor-Binding Protein 3 Expression Increases during Immortalization of Cervical Keratinocytes by Human Papillomavirus Type 16 E6 and E7 Proteins Am. J. Pathol., August 1, 2002; 161(2): 603 - 610. [Abstract] [Full Text] [PDF]
|
|