Human papillomavirus 16 E6 and E7 are associated with the nuclear matrix of cervical carcinoma cells

1997 ◽  
Author(s):  
H Yam ◽  
H Chen ◽  
L Yang ◽  
S Wang ◽  
S ChengChew ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Carcinoma ◽  
Nuclear Matrix ◽  
Carcinoma Cells ◽  
Human Papillomavirus 16 ◽  
E6 And E7

scholarly journals Endogenous Human Papillomavirus E6 and E7 Proteins Differentially Regulate Proliferation, Senescence, and Apoptosis in HeLa Cervical Carcinoma Cells

2003 ◽  
Vol 77 (2) ◽  
pp. 1551-1563 ◽  
Author(s):  
Rosa Anna DeFilippis ◽  
Edward C. Goodwin ◽  
Lingling Wu ◽  
Daniel DiMaio
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Cells ◽  
Cervical Carcinoma ◽  
Carcinoma Cells ◽  
Rb Pathway ◽  
Cervical Cancer Cells ◽  
E6 And E7 ◽  
E7 Proteins ◽  
E6 Protein

ABSTRACT Cervical cancer cells express high-risk human papillomavirus (HPV) E6 and E7 proteins, and repression of HPV gene expression causes the cells to cease proliferation and undergo senescence. However, it is not known whether both HPV proteins are required to maintain the proliferative state of cervical cancer cells, or whether mutations that accumulate during carcinogenesis eliminate the need for one or the other of them. To address these questions, we used the bovine papillomavirus E2 protein to repress the expression of either the E6 protein or the E7 protein encoded by integrated HPV18 DNA in HeLa cervical carcinoma cells. Repression of the E7 protein activated the Rb pathway but not the p53 pathway and triggered senescence, whereas repression of the E6 protein activated the p53 pathway but not the Rb pathway and triggered both senescence and apoptosis. Telomerase activity, cyclin-dependent kinase activity, and expression of c-myc were markedly inhibited by repression of either E6 or E7. These results demonstrate that continuous expression of both the E6 and the E7 protein is required for optimal proliferation of cervical carcinoma cells and that the two viral proteins exert distinct effects on cell survival and proliferation. Therefore, strategies that inhibit the expression or activity of either viral protein are likely to inhibit the growth of HPV-associated cancers.

scholarly journals Repression of the Human Papillomavirus E6 Gene Initiates p53-Dependent, Telomerase-Independent Senescence and Apoptosis in HeLa Cervical Carcinoma Cells

2004 ◽  
Vol 78 (8) ◽  
pp. 4063-4073 ◽  
Author(s):  
Stacy M. Horner ◽  
Rosa Anna DeFilippis ◽  
Laertes Manuelidis ◽  
Daniel DiMaio
Keyword(s):  
Human Papillomavirus ◽  
Tumor Suppressor ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Telomerase Activity ◽  
Carcinoma Cells ◽  
Dominant Negative ◽  
P53 Signaling ◽  
E6 Gene ◽  
E6 And E7

ABSTRACT Cervical cancer cells express high-risk human papillomavirus (HPV) E6 and E7 proteins. When both HPV oncogenes are repressed in HeLa cervical carcinoma cells, the dormant p53 and retinoblastoma (Rb) tumor suppressor pathways are activated, and the cells undergo senescence in the absence of apoptosis. When the E6 gene is repressed in cells that continue to express an E7 gene, the p53 pathway, but not the Rb pathway, is activated, and both senescence and apoptosis are triggered. To determine the role of p53 signaling in senescence or apoptosis after repression of HPV oncogenes, we introduced a dominant-negative allele of p53 into HeLa cells. Dominant-negative p53 prevented senescence and apoptosis when E6 alone was repressed but did not inhibit senescence when both E6 and E7 were repressed. To determine whether reduced telomerase activity was involved in senescence or apoptosis after E6 repression, we generated HeLa cells stably expressing an exogenous hTERT gene, which encodes the catalytic subunit of telomerase. Although these cells contained markedly elevated telomerase activity and elongated telomeres, hTERT expression did not prevent senescence and apoptosis when E6 alone was repressed. These results demonstrate that when the Rb tumor suppressor pathway is inactivated by the E7 protein, E6 repression activates p53 signaling, which in turn is required for growth inhibition, senescence, and apoptosis. Thus, sustained inactivation of the p53 pathway by the E6 protein is required for maintenance of the proliferative phenotype of HeLa cervical carcinoma cells.

scholarly journals Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

Virology ◽  
2012 ◽  
Vol 422 (1) ◽  
pp. 114-124 ◽  
Author(s):  
Thomas G. Magaldi ◽  
Laura L. Almstead ◽  
Stefania Bellone ◽  
Edward G. Prevatt ◽  
Alessandro D. Santin ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Carcinoma ◽  
Carcinoma Cells ◽  
Human Cervical Carcinoma ◽  
E6 And E7 ◽  
Human Cervical Carcinoma Cells
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