Gene expression profile associated with the PDZ ligand-motif of HPV16-E6 oncoprotin in the skin of transgenic mice models
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE22417 | GEO | 2010/07/27
SECONDARY ACCESSION(S): PRJNA128563
REPOSITORIES: GEO
Similar Datasets
Project description:The K14E6 transgenic mice developskin hyperplasia,benign tumors and skin cancer. The tumor formation capacity diminishes when E6 lacks its PDZ ligand-motif. This study aims to compare the transciptional profiles of transgenic K14E6 mice with K14E6 Δ146-151 (lacking the PDZ domain) in order to explore the role of PDZ in early skin carcinogenesis. Skin tissue from three different strains of mice were dissected for RNA extraction, processing and hybridization in Affymetrix Mouse Genome 430 2,0 array. We processed three biological replicates per strain. 3 mice were used for each replicate pool for a final RNA concentration of 3 micrograms. The arrays were analyzed using Partek Genomics suite software.
2010-07-27 | E-GEOD-22417 | biostudies-arrayexpress
Project description:The K14E6 transgenic mice develop skin hyperplasia, benign tumors, and cancer in the dorsal skin spontaneously. The E6 oncoprotein own its tumorigenic potential to a region located near the C-Terminal domain, better known as the PDZ ligand-domain. The aim of this work was to describe early cellular processes affected by the E6’s PDZ ligand-domain when is expressed in the skin of transgenic mice using microarray technology. Results. A total of 222 genes were differentially expressed (FC:1.5, Adj.p.value <0.05, and b value > 0.5) in the skin of K14E6 mice as compared to K14E6Δ146-151 mice. Out of those, 70 genes were up-regulated and 151 genes were down-regulated. Enzyme linked receptor protein signaling was the most affected process in our data, followed by cell adhesion, development, and lipid biosynthesis. We also found that the K14E6 strains induces the mRNA of the wound-inducible gene K6b, and delocalizes E-cadherin protein in the entire epidermis. Finally, CD34 and K15 epidermal stem cell marker proteins diminish its expression in the skin, in a PDZ-dependent manner. Conclusions. The PDZ ligand-domain of HPV16-E6 oncoprotein affects the expression of several genes involved in cellular processes that could be relevant in the HPV-induced carcinogenesis. Since HPV16-E6 oncoproteins lacking the PDZ ligand-domain loose its oncogenic potential, the knowledge of genes transcriptionally affected by the E6’s PDZ ligand-domain will provide valuable information about HPV-induced skin carcinogenesis.
2017-11-30 | GSE99868 | GEO
Project description:Identification of genetic/cytogenetic alterations and differentially expressed cellular genes in HPV16 E6, E7 and E6/E7 positive human foreskin keratinocytes Keywords: ordered
2013-11-27 | GSE14051 | GEO
Project description:Background The in vivo properties of HR-HPV E6 and E7 oncoproteins have been previously evaluated through the generation and characterization of HPV transgenic mouse strains. Although K14E6 transgenic mice develop spontaneous tumors of the skin epithelium, no spontaneous reproductive tract malignancies arise, unless the transgenic mice were treated chronically with 17β-estradiol. Taken together, these findings suggest that E6 performs critical functions in normal adult cervix and skin, highlighting the need to define E6-controlled transcriptional programs in these tissues. We evaluated the different expression profile of 14,000 genes in skin or cervix from young K14E6 transgenic mice compared with corresponding tissues from non-transgenic (FVB) mice. Result Microarray analysis identified a total of 676 and 1154 genes that were significantly up and down-regulated, respectively, in skin from K14E6 transgenic mice. On the other hand, in cervix from K14E6 transgenic mice we found that only 97 and 252 genes were significantly up and down-regulated, respectively. One of the most affected processes in the skin from K14E6 transgenic mice was the cell cycle. We also found that skin from transgenic mice showed down-regulation in pro-apoptotic genes expression, particularly in those related to the extrinsic apoptotic pathway. In contrast, we observed up-regulation of anti-apoptotic genes. Another pathway that was severely affected in skin was the immune response. In cervix from transgenic mice, we could not find affected any gene related to the cell cycle and apoptosis pathways. Interestingly, we observed alterations in the expression of immune response genes in cervix from K14E6 transgenic mice. Pathways such as angiogenesis, cell junction, cytoskeleton, keratinocyte differentiation and epidermis development, showed different gene expression in skin or cervix from K14E6 transgenic mice. Conclusion Alterations in gene expression identified in the current study might partially explain why our K14E6 transgenic mice present a more aggressive phenotype in the skin than in the cervix. Expression of the HPV16 E6 oncoprotein alters expression of genes that fell into several functional groups providing insights into pathways by which E6 deregulate cell cycle progression, apoptosis and the host resistance to infection and immune function, providing new opportunities for early diagnostic markers and therapeutic drug targets. Keywords: Human_papillomavirus, transgenic mice, expression profile
2008-09-01 | GSE10702 | GEO
Project description:Identification of genetic/cytogenetic alterations and differentially expressed cellular genes in HPV16 E6, E7 and E6/E7 positive human foreskin keratinocytes Keywords: ordered We used microarrays to identify differentially expressed genes in human foreskin keratinocytes (HFK) transfected with retroviral vectors harboring the human papillomavirus type 16 oncogenes E6, E7, or E6/E7 in comparison to HFK containing the empty vector control pLXSN.
2013-11-27 | E-GEOD-14051 | biostudies-arrayexpress
Project description:Background; The in vivo properties of HR-HPV E6 and E7 oncoproteins have been previously evaluated through the generation and characterization of HPV transgenic mouse strains. Although K14E6 transgenic mice develop spontaneous tumors of the skin epithelium, no spontaneous reproductive tract malignancies arise, unless the transgenic mice were treated chronically with 17β-estradiol. Taken together, these findings suggest that E6 performs critical functions in normal adult cervix and skin, highlighting the need to define E6-controlled transcriptional programs in these tissues. We evaluated the different expression profile of 14,000 genes in skin or cervix from young K14E6 transgenic mice compared with corresponding tissues from non-transgenic (FVB) mice. Result; Microarray analysis identified a total of 676 and 1154 genes that were significantly up and down-regulated, respectively, in skin from K14E6 transgenic mice. On the other hand, in cervix from K14E6 transgenic mice we found that only 97 and 252 genes were significantly up and down-regulated, respectively. One of the most affected processes in the skin from K14E6 transgenic mice was the cell cycle. We also found that skin from transgenic mice showed down-regulation in pro-apoptotic genes expression, particularly in those related to the extrinsic apoptotic pathway. In contrast, we observed up-regulation of anti-apoptotic genes. Another pathway that was severely affected in skin was the immune response. In cervix from transgenic mice, we could not find affected any gene related to the cell cycle and apoptosis pathways. Interestingly, we observed alterations in the expression of immune response genes in cervix from K14E6 transgenic mice. Pathways such as angiogenesis, cell junction, cytoskeleton, keratinocyte differentiation and epidermis development, showed different gene expression in skin or cervix from K14E6 transgenic mice. Conclusion; Alterations in gene expression identified in the current study might partially explain why our K14E6 transgenic mice present a more aggressive phenotype in the skin than in the cervix. Expression of the HPV16 E6 oncoprotein alters expression of genes that fell into several functional groups providing insights into pathways by which E6 deregulate cell cycle progression, apoptosis and the host resistance to infection and immune function, providing new opportunities for early diagnostic markers and therapeutic drug targets. Experiment Overall Design: We compared the expression paterns in the skin and cervix of K14E6 transgenic mice against the same tissues from non-transgenic FVB mice. For each tissue, we pooled total RNA from three different 6 week virgin mice. Total RNA from the cervix and lower reproductive tract and dorsal skin were obtained from fresh frozen tissue using Trizol. Total RNA was processed an hybridized onto Affymetrix Mouse Genome 430A 2.0 Arrays. For each sample, a technical replica was included.
2008-10-25 | E-GEOD-10702 | biostudies-arrayexpress
Project description:The infection with high-risk human papillomavirus is aetiologically linked to cervical cancer, the role of miRNAs regulated by virus oncogene in cancer progression remain largely unknown. Here, we screened the differentially expressed miRNAs with miRNA array between virus oncogene e6/e7 silenced and not in HPV16-positive cervical cancer cell lines In the study, we screened the differentially expressed miRNAs with miRNA array (Exiqon, miRCURY LNA microRNA array, 7th gen [hsa, miRBase 18]) between virus oncogene e6/e7 silenced and not in HPV16-positive cervical cancer cell lines to found miRNAs regulated by virus oncogene e6/e7. Biological replicates: 3 control, 3 e6/e7 silenced, independently grown and harvested. four replicates per array.
2016-07-01 | E-GEOD-68153 | biostudies-arrayexpress
Project description:The human papillomavirus virus (HPV) is a proven cause of most human cervical cancers, and might have a role in other malignancies including vulva, skin, oesophagus, head and neck cancer. HPV has also been speculated to have a role in the pathogenesis of lung cancer. To validate the hypothesis of HPV involvement in small cell lung cancer pathogenesis we performed gene expression profile of transgenic mouse model of SCLC induced by HPV-16 E6/E7 oncoproteins. Gene expression profile of SCLC has been performed using Agilent whole mouse genome (4x44k) representing ~ 41000 genes and mouse transcripts. Samples were obtained from two HPV16-E6/E7 transgenic mouse model and from littermateM-bM-^@M-^Ys normal lung.
2014-05-27 | E-GEOD-23962 | biostudies-arrayexpress
Project description: Not available
| S-EPMC5654334 | biostudies-literature
Project description:Human papillomavirus (HPV) genome integration into the host genome, blocking E2 expression and leading to overexpression of E6 and E7 viral oncogenes, is considered a major step in cervical cancer development. In high-risk HPVs, E6 and E7 oncogenes are expressed as a bicistronic pre-mRNA, with alternative splicing producing the ultimate mRNAs required for E6 and E7 translation. Given the number of alternative donor and acceptor splicing sites, ten E6/E7 different alternative transcripts might be formed for HPV16 and three for HPV18, although only six isoforms have been previously reported for HPV16. In the present work, we employ high-throughput sequencing of invasive cervical cancer transcriptome (RNA-Seq) to characterize the expression of the HPV genome in 24 invasive cervical cancers associated with HPV16 and HPV18 single infections. Based on high-resolution transcriptional maps, we herein report three viral gene expression patterns which might be associated with the presence of the viral genome in episomal and/or integrated stages. Alternative mRNAs splicing isoforms coding for E6 and E7 oncoproteins were characterized and quantified, and two novel isoforms were identified. Three major isoforms (E6*I, E6*II, and E6+E7) were detected for HPV16 and two for HPV18 (E6*I and E6+E7). Minor transcript isoforms, including the novel ones, were very rare in some tumor samples or were not detected. Our data suggested that minor transcript isoforms of E6/E7 do not play a relevant role in cervical cancer.
2019-08-06 | GSE91065 | GEO