Disease relevance of Human papillomavirus 16

• Samples collected at enrollment from 292 persons in whom squamous-cell carcinoma of the head and neck developed, on average, 9.4 years after enrollment and from 1568 matched controls were analyzed for antibodies against HPV-16, HPV-18, HPV-33, and HPV-73 and for cotinine levels as a marker of smoking habits [1].
• Transient expression of proteins HPV-16 E7, adenovirus type 5 E1A, and SV40 large T antigen is demonstrated to block TGF-beta 1 suppression of c-myc transcription [2].
• Here we provide evidence for the oncogenic transformation of primary cells with a combination of HPV-16 DNA, but not HPV-11 DNA, and the activated form of the human Ha-ras oncogene only in the presence of the glucocorticoid hormone dexamethasone [3].
• The establishment of HPV-6 and BPV-1 E6-immortalized cells was less efficient and required a longer period in comparison to HPV-16 E6 [4].
• The upstream regulatory region of the human papilloma virus-16 (HPV-16) genomic DNA contains a sequence element with a large degree of homology to the partially palindromic sequence GGTACANNNTGTTCT, which is the consensus sequence of the glucocorticoid responsive elements of known genes regulated by this steroid hormone [5].

High impact information on Human papillomavirus 16

• The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53 [6].
• Insight into the mechanism by which E6 functions in oncogenesis is provided by the observation that the E6 protein encoded by HPV-16 and HPV-18 can complex the wild-type p53 protein in vitro [7].
• This activation was observed in cells pre-crisis, that is, before they became immortal, and occurred within one passage of retroviral infection with vectors expressing HPV-16 E6 [8].
• Normal human fibroblasts depleted of functional p53 by SV40 T antigen or HPV-16 E6, and primary embryo fibroblasts from p53 null mice showed seven- to ninefold increased cytotoxicity by paclitaxel [9].
• We show here that expression of the HPV-16 E1-E4 protein in human keratinocytes (the natural host cell for HPV infection) results in the total collapse of the cytokeratin matrix [10].

Chemical compound and disease context of Human papillomavirus 16

• However, red blood cell folate levels at or below 660 nmol/L interacted with HPV-16 infection [11].
• A 400-bp DNA segment centrally containing this sequence confers strong inducibility by dexamethasone to the promoter p97 of HPV-16 and to the Herpes simplex virus thymidine kinase promoter, as judged by chloramphenicol acetyltransferase activity and RNase protection assays [5].
• Replacement of the arginine at position 4 of the HPV-6 E7 protein with an aspartate present in HPV-16 E7 slowed the mobility of the protein when expressed in vivo [12].
• CpG ODN and sorbitol also enhanced the presentation of Db-restricted cytotoxic T lymphocyte epitopes to HPV 16 L1- or E7-specific T lymphocytes after loading of CVLPs onto BMDCs [13].
• In contrast, dominant negative p53 or ectopic HPV 16 E6 sensitized the cells to cisplatin [14].

Biological context of Human papillomavirus 16

• Altered cell cycle regulation in the lens of HPV-16 E6 or E7 transgenic mice: implications for tumor suppressor gene function in development [15].
• Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein [16].
• TEF-1 and its associated co-activator are thus part of a complex mechanism which determines the restricted cell range of the HPV-16 E6 and E7 oncogene promoter [17].
• Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis [18].
• These results define two distinct activities for the HPV-16 E2 protein, indicate functional differences with the BPV E2 protein and suggest that splicing of the HPV E2 mRNA is a critical mechanism for controlling viral gene expression [19].

Anatomical context of Human papillomavirus 16

• Synthetic peptides consisting of DRAHYNI linked to major B-cell epitopes on the E7 molecule formed immunogens capable of eliciting strong antibody responses to HPV-16 E7 [20].
• In the current study, we tested these recombinant vaccinia for in vivo protection against an E7+ tumor, TC-1, which was derived from primary epithelial cells of C57BL/6 mice cotransformed with HPV-16 E6 and E7 and c-Ha-ras oncogenes [21].
• Over the FU period (10-34 months), the level of E7-induced interleukin 2 production from the lymphocytes of CIN patients who had cleared HPV-16 infection showed an inverse correlation with time relative to the last positive HPV DNA test, with 8 of 13 of these patients showing positive responses after clearance [22].
• Induction of specific CD8+ T-lymphocyte responses using a human papillomavirus-16 E6/E7 fusion protein and autologous dendritic cells [23].
• We have studied the role of the HPV-16 E5 protein in apoptosis, using HaCaT cell lines stably transfected with either E5 (HaCaT/E5) or the empty vector (HaCaT/pMSG) as control [24].

Gene context of Human papillomavirus 16

• We find that the HPV-16 E7 protein associates very efficiently with the E2F-cyclin A complex [25].
• Moreover, enhanced degradation of wild-type p53 protein in NSCLC cells expressing human papillomavirus-16 E6 oncoprotein blocked CD437-induced Fas expression [26].
• Sensitivity to the cytotoxic and mutagenic effect of DDP was assessed using a panel of sublines of the MMR-deficient HCT116 colon carcinoma cells in which MMR function had been restored by transfer of a copy of MLH1 on chromosome 3 or in which p53 function had been disabled by expression of HPV-16 E6 [27].
• The results reveal a unique cross-talk between the distinct AP-1- and hormone-signaling pathways, suggesting the involvement of a complex interaction of c-jun and c-fos and glucocorticoid hormone receptor with the HPV 16 cGRE, resulting in novel control patterns for regulating viral expression [28].
• In cells expressing high levels of EGFR plus HPV-16 E5 we found a dramatically increased proliferative activity in soft-agar assays in the presence of EGF [29].

Analytical, diagnostic and therapeutic context of Human papillomavirus 16

• The concordant detection of HPV 16 and 18 DNA between nested PCR and ISH method was 73 and 85.5%, respectively [30].
• In addition, the existence and expression of HPV 16 E6/E7 genes were detected in the lesions induced by ZE67 but not in the lesions of the control mice by analysis by polymerase chain reaction and mRNA in situ hybridization [31].
• In a series of 123 unselected squamous cell carcinomas of the head and neck (SCCHN), we performed sequence analysis of the entire coding region of p53 transcript and determined the presence of the E6 transcripts of HPV 16 and 18 [32].
• We suppressed p53 expression by retroviral-mediated expression of human papillomavirus type-16 E6 protein (HPV-16 E6) in human mammary epithelial cells (HMECs) to develop an in vitro model of tamoxifen chemoprevention in the context of p53 loss [33].
• Weak cross-reactivity of some mAb with the E6 MS2-replicase fusion protein of HPV 16 was detected by ELISA, but no protein of the appropriate size was immunoprecipitated from CaSki cells [34].

References