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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
1997-5-29
|
| pubmed:abstractText |
Cervical cancer is the second leading cause of death from cancer in women worldwide, and recent epidemiological studies have strongly implicated the sexually transmitted human papillomavirus (HPV) as a causative agent. The ability of high-risk HPVs to contribute to malignant progression seems to depend on expression of the viral E6 and E7 oncogenes. The E6 oncoprotein forms a complex with the cellular tumor suppressor protein p53, leading to degradation of p53 via ubiquitin-dependent proteolysis. Thus, E6 expression results in the loss of p53 function in cells, including stimulation of apoptosis and inhibition of the expression of the antiapoptotic protein bcl-2. Recently, we found increased bcl-2 expression in cervical carcinoma cell lines containing mutated or E6-inactivated p53 (X. L. Liang, S. Mungal, A. Ayscue, J. D. Meissner, P. Wodnicki, G. Gordon, S. Lockett, and B. Herman. J. Cell. Biochem., 57: 509-520, 1995). Based on these findings, we examined Papanicolaou smears from 94 women with varying degrees of cervical disease for the presence or absence of p53, HPV-16/18 E6, and bcl-2 proteins using immunofluorescence microscopy. Our findings indicate that there is a statistically significant, inverse association between the presence of p53 and invasive cervical disease [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7]. Moreover, the odds of being diagnosed with an invasive stage of cervical cancer were 3.7 times higher (95% CI, 1.6-8.8) for women positive for the E6 protein and 17 times higher (95% CI, 5.5-58.3) for women positive for the bcl-2 protein compared with women negative for E6 and bcl-2. Women with invasive cervical cancer were also 4.59 times more likely to test positive for the presence of more than one marker (95% CI, 1.8-11.8). Chi(2) analysis demonstrated a strong association between the presence of E6 and bcl-2 (P < 0.001) as well as between the presence of E6 of bcl-2 and diagnosis (P = 0.015 and < 0.001, respectively). In the multivariate analysis, the presence of bcl-2 (OR, 18.8; 95% CI, 5.5-67.8) and age at diagnosis (> or = 50 years; OR, 7.8; 95% CI, 2.5-24.5) showed significant association with Invasive cervical disease. These findings indicate that: (a) the presence of the bcl-2 protein is strongly associated with the development of invasive cervical disease: (b) the pattern of the presence of high-risk HPV-E6, p53, and bcl-2 proteins may be useful for identifying women at increased risk for the development of invasive cervical cancer; and (c) a defect in apoptosis may partially underlie the development of cervical cancer.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E6 protein, Human papillomavirus...,
http://linkedlifedata.com/resource/pubmed/chemical/E6 protein, Human papillomavirus...,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
1055-9965
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
5
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
329-35
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9162297-Adult,
pubmed-meshheading:9162297-Aged,
pubmed-meshheading:9162297-Apoptosis,
pubmed-meshheading:9162297-Carcinoma,
pubmed-meshheading:9162297-Cause of Death,
pubmed-meshheading:9162297-Cell Transformation, Neoplastic,
pubmed-meshheading:9162297-DNA-Binding Proteins,
pubmed-meshheading:9162297-Disease Progression,
pubmed-meshheading:9162297-Female,
pubmed-meshheading:9162297-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:9162297-Gene Expression Regulation, Viral,
pubmed-meshheading:9162297-Humans,
pubmed-meshheading:9162297-Microscopy, Fluorescence,
pubmed-meshheading:9162297-Middle Aged,
pubmed-meshheading:9162297-Mutation,
pubmed-meshheading:9162297-Neoplasm Invasiveness,
pubmed-meshheading:9162297-Oncogene Proteins, Viral,
pubmed-meshheading:9162297-Oncogenes,
pubmed-meshheading:9162297-Papillomaviridae,
pubmed-meshheading:9162297-Papillomavirus Infections,
pubmed-meshheading:9162297-Protein-Tyrosine Kinases,
pubmed-meshheading:9162297-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:9162297-Repressor Proteins,
pubmed-meshheading:9162297-Tumor Suppressor Protein p53,
pubmed-meshheading:9162297-Tumor Virus Infections,
pubmed-meshheading:9162297-Ubiquitins,
pubmed-meshheading:9162297-Uterine Cervical Neoplasms,
pubmed-meshheading:9162297-Vaginal Smears
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer.
|
| pubmed:affiliation |
Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina at Chapel Hill, 27599-7090, USA.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|