Protection against human papillomavirus type 16-E7 oncogene-induced tumorigenesis by in vivo expression of dominant-negative c-jun

2002 ◽  
Vol 34 (2) ◽  
pp. 72-77 ◽  
Author(s):  
Matthew R. Young ◽  
Linda Farrell ◽  
Paul Lambert ◽  
Parirokh Awasthi ◽  
Nancy H. Colburn
Keyword(s):  
Human Papillomavirus ◽  
Dominant Negative ◽  
Human Papillomavirus Type 16 ◽  
In Vivo Expression ◽  
E7 Oncogene

scholarly journals Recapitulation of the Effects of the Human Papillomavirus Type 16 E7 Oncogene on Mouse Epithelium by Somatic Rb Deletion and Detection of pRb-Independent Effects of E7 In Vivo

2003 ◽  
Vol 23 (24) ◽  
pp. 9094-9103 ◽  
Author(s):  
Scott J. Balsitis ◽  
Julien Sage ◽  
Stefan Duensing ◽  
Karl Münger ◽  
Tyler Jacks ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Transgenic Mice ◽  
Biological Activities ◽  
Human Papillomavirus Type 16 ◽  
Retinoblastoma Tumor Suppressor ◽  
Hpv E7 ◽  
Independent Effects ◽  
Retinoblastoma Tumor ◽  
E7 Oncogene

ABSTRACT Although the human papillomavirus (HPV) E7 oncogene is known to contribute to the development of human cervical cancer, the mechanisms of its carcinogenesis are poorly understood. The first identified and most recognized function of E7 is its binding to and inactivation of the retinoblastoma tumor suppressor (pRb), but at least 18 other biological activities have also been reported for E7. Thus, it remains unclear which of these many activities contribute to the oncogenic potential of E7. We used a Cre-lox system to abolish pRb expression in the epidermis of transgenic mice and compared the outcome with the effects of E7 expression in the same tissue at early ages. Mice lacking pRb in epidermis showed epithelial hyperplasia, aberrant DNA synthesis, and improper differentiation. In addition, Rb-deleted epidermis (i.e., epidermis composed of cells with Rb deleted) exhibited centrosomal abnormalities and failed to arrest the cell cycle in response to ionizing radiation. Transgenic mice expressing E7 in skin display the same range of phenotypes. In sum, few differences were detected between Rb-deleted epidermis and E7-expressing epidermis in young mice. However, when both E7 was expressed and Rb was deleted in the same tissue, increased hyperplasia and dysplasia were observed. These findings indicate that inactivation of the Rb pathway can largely account for E7's phenotypes at an early age, but that pRb-independent activities of E7 are detectable in vivo.

scholarly journals Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues.

1991 ◽  
Vol 87 (6) ◽  
pp. 2132-2141 ◽  
Author(s):  
J M Palefsky ◽  
B Winkler ◽  
J P Rabanus ◽  
C Clark ◽  
S Chan ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Human Papillomavirus Type 16 ◽  
Cervical Biopsy ◽  
In Vivo Expression

Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells

1994 ◽  
Vol 14 (2) ◽  
pp. 961-969
Author(s):  
A J Klingelhutz ◽  
S A Barber ◽  
P P Smith ◽  
K Dyer ◽  
J K McDougall
Keyword(s):  
Human Papillomavirus ◽  
Epithelial Cells ◽  
Telomere Length ◽  
Open Reading Frames ◽  
Population Doubling ◽  
Telomere Shortening ◽  
Human Papillomavirus Type 16 ◽  
Immortalized Cells ◽  
E6 And E7

Loss of telomeres has been hypothesized to be important in cellular senescence and may play a role in carcinogenesis. In this study, we have measured telomere length in association with the immortalization and transformation of human cervical and foreskin epithelial cells by the human papillomavirus type 16 or 18 E6 and E7 open reading frames. By using a telomeric TTAGGG repeat probe, it was shown that the telomeres of precrisis normal and E6-, E7-, and E6/E7-expressing cells gradually shortened with passaging (30 to 100 bp per population doubling). Cells that expressed both E6 and E7 went through a crisis period and gave rise to immortalized lines. In contrast to precrisis cells, E6/E7-immortalized cells generally showed an increase in telomere length as they were passaged in culture, with some later passage lines having telomeres that were similar to or longer than the earliest-passage precrisis cells examined. No consistent association could be made between telomere length and tumorigenicity of cells in nude mice. However, of the three cell lines that grew in vivo, two had long telomeres, thus arguing against the hypothesis that cancer cells favor shortened telomeres. Our results indicate that arrest of telomere shortening may be important in human papillomavirus-associated immortalization and that restoration of telomere length may be advantageous to cells with regard to their ability to proliferate.

A DNA vaccine based on a shuffled E7 oncogene of the human papillomavirus type 16 (HPV 16) induces E7-specific cytotoxic T cells but lacks transforming activity

Vaccine ◽  
2001 ◽  
Vol 19 (30) ◽  
pp. 4276-4286 ◽  
Author(s):  
Wolfram Osen ◽  
Tanja Peiler ◽  
Peter Öhlschläger ◽  
Sandra Caldeira ◽  
Stefan Faath ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
Dna Vaccine ◽  
Cytotoxic T Cells ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Transforming Activity ◽  
E7 Oncogene

Studies on in Vivo Induction of Cytotoxic T Lymphocyte Responses by Synthetic Peptides from E6 and E7 Oncoproteins of Human Papillomavirus Type 16

1995 ◽  
Vol 8 (3) ◽  
pp. 165-174 ◽  
Author(s):  
ASIS K. SARKAR ◽  
GUILLERMO TORTOLERO-LUNA ◽  
PRAMOD N. NEHETE ◽  
RALPH B. ARLINGHAUS ◽  
MICHELE FOLLEN MITCHELL ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
T Lymphocyte ◽  
Synthetic Peptides ◽  
Cytotoxic T Lymphocyte ◽  
Human Papillomavirus Type 16 ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7 ◽  
Lymphocyte Responses ◽  
In Vivo Induction

scholarly journals In vivo expression of mammalian BiP ATPase mutants causes disruption of the endoplasmic reticulum.

1995 ◽  
Vol 6 (3) ◽  
pp. 283-296 ◽  
Author(s):  
L M Hendershot ◽  
J Y Wei ◽  
J R Gaut ◽  
B Lawson ◽  
P J Freiden ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Binding ◽  
Point Mutations ◽  
Binding Domain ◽  
Dominant Negative ◽  
Atp Binding ◽  
Heavy Chains ◽  
In Vivo Expression

BiP possesses ATP binding/hydrolysis activities that are thought to be essential for its ability to chaperone protein folding and assembly in the endoplasmic reticulum (ER). We have produced a series of point mutations in a hamster BiP clone that inhibit ATPase activity and have generated a species-specific anti-BiP antibody to monitor the effects of mutant hamster BiP expression in COS monkey cells. The enzymatic inactivation of BiP did not interfere with its ability to bind to Ig heavy chains in vivo but did inhibit ATP-mediated release of heavy chains in vitro. Immunofluorescence staining and electron microscopy revealed vesiculation of the ER membranes in COS cells expressing BiP ATPase mutants. ER disruption was not observed when a "44K" fragment of BiP that did not include the protein binding domain was similarly mutated but was observed when the protein binding region of BiP was expressed without an ATP binding domain. This suggests that BiP binding to target proteins as an inactive chaperone is responsible for the ER disruption. This is the first report on the in vivo expression of mammalian BiP mutants and is demonstration that in vitro-identified ATPase mutants behave as dominant negative mutants when expressed in vivo.

scholarly journals Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells.

1994 ◽  
Vol 14 (2) ◽  
pp. 961-969 ◽  
Author(s):  
A J Klingelhutz ◽  
S A Barber ◽  
P P Smith ◽  
K Dyer ◽  
J K McDougall
Keyword(s):  
Human Papillomavirus ◽  
Epithelial Cells ◽  
Telomere Length ◽  
Open Reading Frames ◽  
Population Doubling ◽  
Telomere Shortening ◽  
Human Papillomavirus Type 16 ◽  
Immortalized Cells ◽  
E6 And E7

Loss of telomeres has been hypothesized to be important in cellular senescence and may play a role in carcinogenesis. In this study, we have measured telomere length in association with the immortalization and transformation of human cervical and foreskin epithelial cells by the human papillomavirus type 16 or 18 E6 and E7 open reading frames. By using a telomeric TTAGGG repeat probe, it was shown that the telomeres of precrisis normal and E6-, E7-, and E6/E7-expressing cells gradually shortened with passaging (30 to 100 bp per population doubling). Cells that expressed both E6 and E7 went through a crisis period and gave rise to immortalized lines. In contrast to precrisis cells, E6/E7-immortalized cells generally showed an increase in telomere length as they were passaged in culture, with some later passage lines having telomeres that were similar to or longer than the earliest-passage precrisis cells examined. No consistent association could be made between telomere length and tumorigenicity of cells in nude mice. However, of the three cell lines that grew in vivo, two had long telomeres, thus arguing against the hypothesis that cancer cells favor shortened telomeres. Our results indicate that arrest of telomere shortening may be important in human papillomavirus-associated immortalization and that restoration of telomere length may be advantageous to cells with regard to their ability to proliferate.

Sign in / Sign up

Export Citation Format

Share Document