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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TA-HPV (therapeutic antigen-human papilloma virus) is a vaccine being developed by Xenova (formerly Cantab) for the potential treatment of cervical cancer. The antigen is intended to activate HPV-specific cytotoxic T-cells to attack tumor cells containing the viral antigen. Over 70% of patients with cervical cancer have tumor cells containing papillomavirus DNA [173070]. TA-HPV has reached phase IIa trials in 60 patients with high-grade anogenital intraepithelial neoplasia, including VIN3 (grade 3 vulvar intraepithelial neoplasia), to evaluate clinical efficacy [381386], [427159], [429895]. In addition, a phase II 'prime-boost' study of TA-HPV in combination with TA-CIN has been initiated at three centers across the UK [427159].
Curr Opin Mol Ther 2001 Dec
PMID:Technology evaluation: T-cell activator, Xenova. 1180 73

In the absence of a causal relationship between the incidence of sporadic breast cancer and occurrence of mutations in breast cancer susceptibility genes, efforts directed to investigating the contribution of environmental xenobiotics in the etiology of sporadic mammary neoplasia are warranted. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants, which have been shown to induce DNA damage and disrupt cell cycle progression. In this report we discuss published data pointing to PAHs as a risk factor in carcinogenesis, and present findings generated in our laboratory suggesting that the mammary tumorigenicity of PAHs may be attributable, at least in part, to disruption of BRCA-1 expression by reactive PAH-metabolites. We report that benzo[a]pyrene (B[a]P), selected as a prototype PAH, disrupts BRCA-1 transcription in estrogen receptor (ER)-positive but not ER-negative breast cancer cells. The reduced potential for BRCA-1 expression in B[a]P-treated cells coincides with disruption of cell cycle kinetics and accumulation of p53. These effects are counteracted by the AhR-antagonist alpha-naphthoflavone (ANF), and in breast cancer cells expressing mutant p53 or the E6 human papilloma virus protein. We suggest that exposure to PAHs may be a predisposing factor in the etiology of sporadic breast cancer by disrupting the expression of BRCA-1.
Environ Mol Mutagen 2002
PMID:Epigenetics of breast cancer: polycyclic aromatic hydrocarbons as risk factors. 1192 Nov 94

hnRNPK and hnRNP E1/E2 mediate translational silencing of cellular and viral mRNAs in a differentiation-dependent way by binding to specific regulatory sequences. The translation of 15-lipoxygenase (LOX) mRNA in erythroid precursor cells and of the L2 mRNA of human papilloma virus type 16 (HPV-16) in squamous epithelial cells is silenced when either of these cells is immature and is activated in maturing cells by unknown mechanisms. Here we address the question of how the silenced mRNA can be translationally activated. We show that hnRNP K and the c-Src kinase specifically interact with each other, leading to c-Src activation and tyrosine phosphorylation of hnRNP K in vivo and in vitro. c-Src-mediated phosphorylation reversibly inhibits the binding of hnRNP K to the differentiation control element (DICE) of the LOX mRNA 3' untranslated region in vitro and specifically derepresses the translation of DICE-bearing mRNAs in vivo. Our results establish a novel role of c-Src kinase in translational gene regulation and reveal a mechanism by which silenced mRNAs can be translationally activated.
Mol Cell Biol 2002 Jul
PMID:c-Src-mediated phosphorylation of hnRNP K drives translational activation of specifically silenced mRNAs. 1205 63

Cervical cancer is known to be highly associated with viral oncogene E6 and E7 of human papilloma virus. Down-regulation of oncogene expression by antisense-based gene therapy has been extensively studied. To investigate the effect of HPV 16 E6 antisense nucleic acid (AS) on cervical cancer cells, human cervical cancer cell lines, CaSki and SiHa cells harboring HPV 16 genome were transfected with plasmid containing E6(AS). The decreased viability and the apoptotic morphology were observed in E6(AS)-transfected cervical cancer cell lines. By 6 h after transfection, inhibition of E6 splicing, rapid upregulations of p53 and a p53-responsive protein, GADD45, were displayed in E6(AS)-transfected CaSki cells. Furthermore, E6(AS) induced loss of mitochondrial transmembrane potential, release of mitochondrial cytochrome c into the cytoplasm, and subsequent activation of caspase-9 and caspase-3. These results indicate that HPV 16 E6(AS) induces apoptosis in CaSki cells via upregulation of p53 and release of cytochrome c into cytoplasm, consequently activating procaspase-9 and procaspase-3.
Exp Mol Med 2002 May 31
PMID:HPV E6 antisense induces apoptosis in CaSki cells via suppression of E6 splicing. 1208 99

To search for potential biomarkers used to monitor the process of immortalization, we investigated the relative level of telomerase activity and other immortal phenotypes in the SHEE esophageal epithelial cell line. This human fetal esophageal epithelial cell line, induced by human papilloma virus (HPV) 18 E6E7, was continually propagated over 100 passages. Fourteenth passage cells (SHEE14) were cultured in a flask with a serum-free medium and continually cultured to the 30th passage (SHEE30). Cells of SHEE14, SHEE20 and SHEE30 were examined according to cell morphology, cell cycle, apoptosis, contact-inhibition growth, anchorage- dependency, dose-dependency to epithelial growth factors (EGF), telomerase activity and tumorigenicity. The SHEE14 cells exhibited good differentiation with contact-inhibition and anchorage-dependent growth. The SHEE20 cells exhibited increase of senescent and apoptotic cells, and difficulty in propagation. The SHEE30 cells exhibited a higher proliferative index and some undifferentiated cells, with weakened contact-inhibition and anchorage-dependent growth. The telomerase was activated in cells of SHEE30, but not in SHEE14 and SHEE20 cells. The different response to dose-dependency to EGF was not statistically different in SHEE14 and SHEE30. Three groups of cells displayed lack of tumor formation in nude mice. Compared with SHEE14 and SHEE20, SHEE30 cells were of immortalized status with immortal phenotype, which consisted of telomerase activity, increase of cell proliferation, weakened contact-inhibition and anchorage-dependent growth, dose dependency to EGF and lack of tumor formation. From passage 14 to 30th passage, SHEE cells went through cellular senescence, apoptosis and immortalization. With a view toward diagnostic and biological aspects, telomerase activity is a crucial step and a cardinal requirement for immortalization. The telomerase activity and other immortal phenotypes are potential markers for monitoring the process of immortalization.
Int J Mol Med 2002 Nov
PMID:Immortal phenotype of the esophageal epithelial cells in the process of immortalization. 1237 8

The human papilloma virus-type 16 (HPV-16) E6 and E7 proteins interact with the p53 and pRb tumor suppressor proteins, respectively. The effect of E6 or E7 expression on UV irradiation (5 and 20 J/m2)-induced genotoxic injury of confluent primary murine astrocytes was determined. Retroviral vectors were used to overexpress E6 and E7. Astrocytes expressing E7 showed increased vulnerability to UV-induced apoptosis while E6 over expressing astrocytes were protected from the same insults. Cell death in the E7 overexpressing cells was apoptotic because it showed DNA ladders, activation of caspase-3, formation of apoptotic bodies and decreased DNA content to less than the G0 level. After UV-irradiation the level of E2F1 in E7-expressing astrocytes was higher than E6-, LXSN- or mock-infected cells, and caspase-3 was activated to a greater extent. E7-expressing astrocytes showed the highest levels of Bax under normal growth conditions. The mitochondrial membrane potential of E7-expressing astrocytes was depolarized by 90% after UV-irradiation while the depolarization in control cells was about 50%. E6 overexpression decreased while E7 overexpression increased UV-induced astrocyte apoptosis.
Mol Cells 2002 Oct 31
PMID:UV-vulnerability of human papilloma virus type-16 E7-expressing astrocytes is associated with mitochondrial membrane depolarization and caspase-3 activation. 1244 3

The prostanoid prostacyclin (PGI2) inhibits aortic smooth muscle cell proliferation by blocking cell cycle progression from G1-to S-phase. However, the mechanism of this inhibition is poorly understood. We report here that the PGI2 mimetic, cicaprost, inhibits the induction of cyclin A and activation of the cyclin A promoter in primary and established rodent aortic smooth muscle cells. The inhibition of cyclin A gene expression is associated with a block in cyclin E-cdk2 activity and phosphorylation of both the retinoblastoma protein and p107. Inactivation of pocket proteins with human papilloma virus protein E7 partially, but not completely, restored cyclin A promoter activity in cicaprost-treated cells. Complementary studies showed that occupancy of the cAMP response element (CRE) is required for efficient activation of the cyclin A promoter in aortic smooth muscle cells, that the CRE is primarily occupied by the CRE-binding protein (CREB) and phospho-CREB, and that cicaprost blocks the binding of CREB and phospho-CREB to the cyclin A promoter CRE. Treatment with pertussis toxin reversed the inhibitory effects of cicaprost on CRE occupancy, cyclin E-cdk2 activity, and S phase entry, suggesting the involvement of Gi signaling in cicaprost action. We conclude that PGI2 inhibits proliferation of aortic smooth muscle cells by coordinately blocking CRE- and pocket protein-dependent cyclin A gene expression.
Mol Pharmacol 2003 Aug
PMID:Prostacylin receptor activation inhibits proliferation of aortic smooth muscle cells by regulating cAMP response element-binding protein- and pocket protein-dependent cyclin a gene expression. 1286 29

CSL, licensee of UniQuest's HPV technology, and Aventis Pasteur MSD (a joint venture between Merck & Co and Aventis) are jointly developing a vaccine for the potential prophylaxis of genital warts and cervical cancer caused by human papilloma virus infection. Enrollment for a phase III trial has been completed.
Curr Opin Mol Ther 2004 Apr
PMID:Technology evaluation: HPV vaccine (quadrivalent), Aventis Pasteur MSD/CSL. 1519 33

It is estimated that 15% of all cancers are etiologically linked to viral infection. Specific cancers including adult T-cell leukemia, hepatocellular carcinoma, and uterine cervical cancer are associated with infection by human T-cell leukemia virus type I, hepatitis B virus, and high-risk human papilloma virus, respectively. In these cancers, genomic instability, a hallmark of multistep cancers, has been explicitly linked to the expression of oncoproteins encoded by these viruses. This review discusses mechanisms utilized by these viral oncoproteins, Tax, HBx, and E6/E7, to mediate genomic instability and cellular transformation.
Environ Mol Mutagen
PMID:Impact of transforming viruses on cellular mutagenesis, genome stability, and cellular transformation. 1564 40

Aim-To describe a method for amplifying human papilloma virus (HPV) in situ hybridisation (ISH) signals.Methods-Three human cervical cell lines, namely CaSKi, HeLa and SiHa, containing different copy numbers of integrated HPV DNA were studied. Following ISH, catalysed reporter deposition (CARD), based on the deposition of biotinylated tyramine at the location of the DNA probe, was used to amplify the ISH signal.Results-Using CARD-ISH, one to three HPV type 16 copies were detected in situ both in cell suspensions and paraffin wax sections of SiHa cells. CARD-ISH can also be used to detect oncogenic HPV DNA sequences, such as HPV types 16 and 18, in routinely processed formalin fixed, paraffin wax embedded cervical specimens.Conclusions-CARD-ISH is a fast and highly sensitive ISH method for the routine detection of low copy number HPV DNA sequences in cervical cell lines and routinely processed tissue sections. Application of this technology also enables the routine detection and cellular localisation of other viral DNA sequences present at copy numbers below the detection limit of conventional ISH methods.
Clin Mol Pathol 1996 Dec
PMID:Human papilloma virus detection by in situ hybridisation signal amplification based on biotinylated tyramine deposition. 1669


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