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Gene expression profiling of cidofovir treatment and resistance inHeLa, HaCaT, and PHK cells

ABSTRACT: Cidofovir is an acyclic nucleoside phosphonate with strong antiviral activity against a broad spectrum of DNA viruses. Although it has previously been shown that cidofovir exerts an antiproliferative effect on HPV positive cells by the induction of apoptosis, the exact mechanism of action remains to be unraveled. In order to study the activity of cidofovir against HPV, gene expression profiling was performed in cidofovir-treated and cidofovir-resistant HeLa, HaCaT, and PHK cells by means of microarrays (HG-U133 Plus 2, Affymetrix). Controls (untreated HeLa, HaCaT, and PHK wild-type cells): 72h of growth. Cidofovir treated (50 M-BM-5g/ml) HeLa, HaCaT, and PHK cells: 72h of growth. Cidofovir resistant cells (HeLa #52 and HaCaT #51): 72h of growth. All samples were performed in triplicates.

ORGANISM(S): Homo sapiens

SUBMITTER: Joke Allemeersch

PROVIDER: E-GEOD-39293 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Cidofovir selectivity is based on the different response of normal and cancer cells to DNA damage.

De Schutter Tim T Andrei Graciela G Topalis Dimitri D Naesens Lieve L Snoeck Robert R

BMC medical genomics 20130523

<h4>Background</h4>Cidofovir (CDV) proved efficacious in treatment of human papillomaviruses (HPVs) hyperplasias. Antiproliferative effects of CDV have been associated with apoptosis induction, S-phase accumulation, and increased levels of tumor suppressor proteins. However, the molecular mechanisms for the selectivity and antitumor activity of CDV against HPV-transformed cells remain unexplained.<h4>Methods</h4>We evaluated CDV drug metabolism and incorporation into cellular DNA, in addition to ...[more]

PMID: 23702334

Similar Datasets

Gene expression profiling of cidofovir treatment and resistance inHeLa, HaCaT, and PHK cells

Project description:Cidofovir is an acyclic nucleoside phosphonate with strong antiviral activity against a broad spectrum of DNA viruses. Although it has previously been shown that cidofovir exerts an antiproliferative effect on HPV positive cells by the induction of apoptosis, the exact mechanism of action remains to be unraveled. In order to study the activity of cidofovir against HPV, gene expression profiling was performed in cidofovir-treated and cidofovir-resistant HeLa, HaCaT, and PHK cells by means of microarrays (HG-U133 Plus 2, Affymetrix).

2013-07-03 | GSE39293 | GEO

Homo sapiens

Project description:HaCaT +GLI1/2 24/72h

| PRJNA89971 | ENA

Expression data from BCL-3 overexpression HaCat cells

Project description:Constitutive activation of EGFR- and NF-kB-dependent pathways is a hallmark of cancer, yet signaling proteins that connect both oncogenic cascades are poorly characterized. Here we define KIAA1199 as a BCL-3- and p65-dependent gene in transformed keratinocytes. KIAA1199 expression is enhanced upon human papillomavirus (HPV) infection and is aberrantly expressed in clinical cases of cervical (pre)neoplastic lesions. Mechanistically, KIAA1199 binds Plexin A2 and protects from Semaphorin 3A-mediated cell death by promoting EGFR stability and signaling. Moreover, KIAA1199 is an EGFR-binding protein and KIAA1199 deficiency impairs EGF-dependent Src, MEK1 and ERK1/2 phosphorylations. Therefore, EGFR stability and signaling to downstream kinases requires KIAA1199. As such, KIAA1199 promotes EGF-mediated epithelial-mesenchymal transition (EMT). Taken together, our data define KIAA1199 as an oncogenic protein induced by HPV infection and constitutive NF-kB activity that transmits pro-survival and invasive signals through EGFR signaling. We used microarrays to detail the global programme of gene expression upon BCL-3 overexpression We used two experimental conditions, namely HaCat cells infected with a control lentivirus as well as HaCat cells infected with a BCL-3 expressing construct. Both experimental conditions were in triplicates.

2014-11-04 | E-GEOD-60551 | biostudies-arrayexpress

Transfection of HaCaT cells with HPV11 HPV16 or HPV45 genome

Project description:We investigated the early stage of HPV infections by global expression profiling in a cell model, in which cells from the human keratinocyte cell line, HaCaT, were transfected with HPV11, HPV16 or HPV45 genomes ( methods used for transfection are described in PubMed ID: 21078297)

2012-07-01 | E-MTAB-1160 | biostudies-arrayexpress

Gene expression characterization of HPV positive head and neck cancer to predict response to Chemoradiation

Project description:Background: Human papillomavirus has been shown to have a causal role in the development of head and neck squamous cell carcinoma and represents a distinct and well-defined pathology. While HPV-positive HNSCC is associated with a better response to treatment and prognosis, a subset of patients do not respond favorably to current standard of care thus suffering unnecessary morbidity and delay to receive effective therapy. Methods: RNA from nineteen patients with HPV-positive HNSCC was subjected to gene expression analysis using Affymetrix microarrays. HPV-status was confirmed by detection of HPV16 E7 with RT-PCR. Results: In addition to specific genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes were highly represented in the cell processes of genomic stability, cell cycle, and DNA damage. Conclusions: This pilot study suggests possible biomarkers that predict response to chemoradiation therapy. These data can potentially lead to an assay that can be used clinically to predict HPV-positive HNSCC patients that will not benefit from chemoradiation, thus helping clinicians to lower morbidity and get selected patients to surgery faster. HPV-positive head and neck squamous cell carcinoma (HNSCC) has a good prognosis with a large percentage of patients responding to therapy. However, a certain percentage of patients do not respond. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare patients that responded to therapy with those that did not respond.

2014-12-19 | E-GEOD-40020 | biostudies-arrayexpress

Incoming human papillomavirus 16 genome is lost in PML protein-deficient HACAT keratinocytes.

Project description:Human papillomaviruses (HPVs) target PML nuclear bodies during infectious entry and PML protein is important for efficient transcription of incoming viral genome.We used shRNA to knockdown PML protein in HaCaT keratinocytes to further investigate the role of PML protein in HPV entry. We used microarrays to compare the transcriptome of PML protein-deficient with vector control-transduced HaCaT cells.

2016-11-17 | GSE89937 | GEO

Time-dependent transcriptomic changes in HNSCC cell lines after irradiation with photons or Carbon ions

Project description:Purpose: We aim to identify irradiation-induced transciptional changes in HPV-positive and HPV-negative HNSCC cell lines in vitro. Methods: Cells were seeded to tissue culture flasks and irradiated after adherence, with 0 Gy or 4 Gy carbon ions or 4 Gy photons or 8 Gy photons. Analysis was performed 4h and 48h and 72h after irradiation Results: Analysis of the data reveals a clear difference between irradiated and unirradiated samples, as well as between HPV-positive and HPV-negative HNSCC cells Conclusion: Transcriptomic changes are dependent on HPV Status and irradiation, but independent from the type of irradiation.

2022-05-11 | GSE198100 | GEO

Expression data from fission yeast deletion mutant of Klf1, a C2H2 zinc finger-transcription factor, in G0 and VE phases

Project description:Fission yeast Schizosaccharomyces pombe is a model for studying cellular quiescence. Shifting to medium without a nitrogen-source induces proliferative cells to enter long-term G0 quiescence. Klf1 is a Kruppel-like transcription factor with a 7-amino acid-spaced C2H2-type zinc finger motif. The deletion mutant M-bM-^HM-^Fklf1 normally divides in vegetative medium, but proliferation is not restored after long-term G0 quiescence. Cell biologic, transcriptomic, and metabolomic analyses revealed a unique phenotype of the M-bM-^HM-^Fklf1 mutant in quiescence. Mutant cells had diminished transcripts related to signaling molecules for switching to differentiation. In contrast, proliferative metabolites for cell-wall assembly and antioxidants significantly increased. Further, the size of the M-bM-^HM-^Fklf1 cells is markedly increased during quiescence due to the aberrant accumulation of calcofluor-positive chitin-like materials beneath the cell wall. After 4 weeks quiescence, the ability for reversible proliferation is lost, but energy metabolism is maintained. Klf1 thus plays a role in G0 phase longevity through enhancing the differentiation signal and suppressing metabolism for growth. If Klf1 is lost, S. pombe fails to maintain a constant cell size during quiescence. Gene expression profile of fission yeast wild type cells and klf1-gene disruptant cells in proliferating state and in quiescent state. Type of experiment: Comparing between wild type cells and klf1-gene disruptant cells in proliferating condition and in quiescent condition. Experimental factor: Exponentially proliferating state in synthetic medium, EMM2, and quiescent G0 state in nitrogen-depleted synthetic medium, EMM2-N. Quality control steps taken: All experiments were repeated twice in each condition.

2013-12-01 | E-GEOD-50986 | biostudies-arrayexpress

Expression data from FIT-039 or Flavopiridol compound treated HeLa cells

Project description:FIT-039 is a novel antiviral compound. Antiviral mechanism of FIT-039 is the inhibition of the viral transcription through suppression of the CTD phosphorylation of RNA polymerase II. We used microarrays to evaluated the effect of FIT-039 on host cellular transcriptome, compared with Flavopiridol which is an existing pan-specific CDK9 inhibitor. HeLa cells were incubated with FIT-039 or flavopiridol at the concentration of IC80 for 24 hr, and cellular RNAs were collected and subjected to microarray analysis. The solvent DMSO was used as a negative control.

2014-07-08 | E-GEOD-57429 | biostudies-arrayexpress

MicroRNA (miRNA) expression of IMCD tubule suspension

Project description:miRNA plays a role as post-transcriptional regulator. However, miRNAs in the kidney collecting duct cell have not been well understood. So we aimed to profile miRNAs in the kidney inner medullary collecting duct (IMCD) cells, and to identify the vasopressin-responsive miRNAs in the kidney IMCD cells. The microarray assay revealed that relative expression of miRNAs in the kidney IMCD cells was changed by desmopressin (dDAVP) stimulation. Fresh IMCD tubules were prepared from rat kidney and incubated in the medium in the absence or presence of dDAVP (1 nM, 2 h). Total RNA purified from IMCD tubules was used to analyze miRNA expression by GeneChipM-BM-. miRNA 3.0 Array (Affymetrix).

2014-06-21 | E-GEOD-58693 | biostudies-arrayexpress

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