Transcriptional control of human papillomavirus type 18 oncogene expression in different cell lines: Role of transcription factor YY1

Virus Genes ◽  
1995 ◽  
Vol 11 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Franziska Jundt ◽  
Ingrid Herr ◽  
Peter Angel ◽  
Harald Zur Hausen ◽  
Tobias Bauknecht
Keyword(s):  
Transcription Factor ◽  
Human Papillomavirus ◽  
Cell Lines ◽  
Transcriptional Control ◽  
Oncogene Expression ◽  
Transcription Factor Yy1

scholarly journals Progression and Differentiation of Alveolar Rhabdomyosarcoma Is Regulated by PAX7 Transcription Factor—Significance of Tumor Subclones

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1870
Author(s):  
Klaudia Skrzypek ◽  
Grażyna Adamek ◽  
Marta Kot ◽  
Bogna Badyra ◽  
Marcin Majka
Keyword(s):  
Transcription Factor ◽  
Cell Lines ◽  
Migration Activity ◽  
Id Proteins ◽  
Rh30 Cell ◽  
Str Profile ◽  
And Migration

Rhabdomyosarcoma (RMS), is the most frequent soft tissue tumor in children that originates from disturbances in differentiation process. Mechanisms leading to the development of RMS are still poorly understood. Therefore, by analysis of two RMS RH30 cell line subclones, one subclone PAX7 negative, while the second one PAX7 positive, and comparison with other RMS cell lines we aimed at identifying new mechanisms crucial for RMS progression. RH30 subclones were characterized by the same STR profile, but different morphology, rate of proliferation, migration activity and chemotactic abilities in vitro, as well as differences in tumor morphology and growth in vivo. Our analysis indicated a different level of expression of adhesion molecules (e.g., from VLA and ICAM families), myogenic microRNAs, such as miR-206 and transcription factors, such as MYOD, MYOG, SIX1, and ID. Silencing of PAX7 transcription factor with siRNA confirmed the crucial role of PAX7 transcription factor in proliferation, differentiation and migration of RMS cells. To conclude, our results suggest that tumor cell lines with the same STR profile can produce subclones that differ in many features and indicate crucial roles of PAX7 and ID proteins in the development of RMS.

scholarly journals Characterization of the BCR promoter in Philadelphia chromosome-positive and -negative cell lines.

1991 ◽  
Vol 11 (4) ◽  
pp. 1854-1860 ◽  
Author(s):  
N P Shah ◽  
O N Witte ◽  
C T Denny
Keyword(s):  
Transcription Factor ◽  
Cell Lines ◽  
Transcription Initiation ◽  
Transcriptional Control ◽  
Philadelphia Chromosome ◽  
Gc Content ◽  
Cellular Transformation ◽  
Nucleotide Sequence Analysis ◽  
Coding Sequences ◽  
Gene Assay

The t(9;22) Philadelphia chromosome translocation fuses 5' regulatory and coding sequences of the BCR gene to the c-ABL proto-oncogene. This results in the formation of hybrid BCR-ABL mRNAs and proteins. The shift in ABL transcriptional control to the BCR promoter may play a role in cellular transformation mediated by this rearrangement. We have functionally localized the BCR promoter to a region 1 kb 5' of BCR exon 1 coding sequences by using a chloramphenicol acetyltransferase reporter gene assay. Nucleotide sequence analysis of this region revealed many consensus binding sequences for transcription factor SP1 as well as two potential CCAAT box binding factor sites and one putative helix-loop-helix transcription factor binding site. No TATA-like or "initiator" element sequences were found. Because of low steady-state levels of BCR mRNA and the high GC content (78%) of the promoter region, definitive mapping of transcription start sites required artificial amplification of BCR promoter-directed transcripts. Overexpression from the BCR promoter in a COS cell system was effective in demonstrating multiple transcription initiation sites. In order to assess the effects of chromosomal translocation on the transcriptional control of the BCR gene, we determined S1 nuclease protection patterns of poly(A)+ RNA from tumor cell lines. No differences were observed in the locations and levels of BCR transcription initiation sites between those lines that harbored the t(9;22) translocation and those that did not. This demonstrates that BCR promoter function remains intact in spite of genomic rearrangement. The BCR promoter is structurally similar to the ABL promoters. Together, this suggests that the structural fusion of BCR-ABL and not its transcriptional deregulation is primarily responsible for the transforming effect of the t(9;22) translocation.

scholarly journals Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma

2020 ◽  
Author(s):  
Shunsuke Kondo ◽  
Hitoshi Hirakawa ◽  
Taro Ikegami ◽  
Takayuki Uehara ◽  
Shinya Agena ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Mtor Pathway ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
High Gene ◽  
Complex Expression

Abstract Background Despite reports of a link between human papillomavirus (HPV) infection and mechanistic target of rapamycin (mTOR) signaling activation, the role of the mTOR pathway, especially raptor and rictor, in HPV-related head and neck cancer is still unclear. The aim of the present study was to elucidate the role of the mTOR pathway in HPV-related oropharyngeal squamous cell carcinoma (OPSCC). Methods The present study involved two strategies. The first was to investigate the activity of mTOR and mTOR-related complexes in high-risk HPV-positive (UM-SCC47 and CaSki) and HPV-negative (SCC-4 and SAS) cancer cell lines. The second was to elucidate mTOR complex expression in 80 oropharyngeal cancer tissues and to examine the relationship between mTOR complex expression and survival in patients with OPSCC. Results The UM-SCC47 and CaSki cell lines showed high gene and protein expression of raptor. They also exhibited G1/S and G2/M phase cell cycle arrest following 24 h incubation with 6 μM temsirolimus, a rapamycin analog, and temsirolimus administration inhibited their growth. HPV-related OPSCC samples showed high gene expression of raptor and rictor compared with HPV-unrelated OPSCC. In addition, HPV-related OPSCC patients with high raptor and rictor expression tended to have a worse prognosis than those with low or medium expression. Conclusions These results suggest that raptor has an important role in HPV-related OPSCC and that temsirolimus is a potential therapeutic agent for patients with HPV-related OPSCC. This is the first report to reveal overexpression of raptor and rictor in HPV-related OPSCC.

scholarly journals Comparative Transcriptomics Highlights the Role of the Activator Protein 1 Transcription Factor in the Host Response to Ebolavirus

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
James W. Wynne ◽  
Shawn Todd ◽  
Victoria Boyd ◽  
Mary Tachedjian ◽  
Reuben Klein ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Lines ◽  
Human Cells ◽  
Activator Protein 1 ◽  
Host Gene Expression ◽  
Rna Seq ◽  
Content Type ◽  
Molecular Events ◽  
Ebov Infection

ABSTRACT Ebolavirus and Marburgvirus comprise two genera of negative-sense single-stranded RNA viruses that cause severe hemorrhagic fevers in humans. Despite considerable research efforts, the molecular events following Ebola virus (EBOV) infection are poorly understood. With the view of identifying host factors that underpin EBOV pathogenesis, we compared the transcriptomes of EBOV-infected human, pig, and bat kidney cells using a transcriptome sequencing (RNA-seq) approach. Despite a significant difference in viral transcription/replication between the cell lines, all cells responded to EBOV infection through a robust induction of extracellular growth factors. Furthermore, a significant upregulation of activator protein 1 (AP1) transcription factor complex members FOS and JUN was observed in permissive cell lines. Functional studies focusing on human cells showed that EBOV infection induces protein expression, phosphorylation, and nuclear accumulation of JUN and, to a lesser degree, FOS. Using a luciferase-based reporter, we show that EBOV infection induces AP1 transactivation activity within human cells at 48 and 72 h postinfection. Finally, we show that JUN knockdown decreases the expression of EBOV-induced host gene expression. Taken together, our study highlights the role of AP1 in promoting the host gene expression profile that defines EBOV pathogenesis. IMPORTANCE Many questions remain about the molecular events that underpin filovirus pathophysiology. The rational design of new intervention strategies, such as postexposure therapeutics, will be significantly enhanced through an in-depth understanding of these molecular events. We believe that new insights into the molecular pathogenesis of EBOV may be possible by examining the transcriptomic response of taxonomically diverse cell lines (derived from human, pig, and bat). We first identified the responsive pathways using an RNA-seq-based transcriptomics approach. Further functional and computational analysis focusing on human cells highlighted an important role for the AP1 transcription factor in mediating the transcriptional response to EBOV infection. Our study sheds new light on how host transcription factors respond to and promote the transcriptional landscape that follows viral infection.

scholarly journals The Pit-1/Pou1f1 transcription factor regulates and correlates with prolactin expression in human breast cell lines and tumors

2010 ◽  
Vol 17 (1) ◽  
pp. 73-85 ◽  
Author(s):  
I Ben-Batalla ◽  
S Seoane ◽  
M Macia ◽  
T Garcia-Caballero ◽  
L O Gonzalez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cell Lines ◽  
Independent Effect ◽  
Breast Cancer Cell Lines ◽  
Transcriptional Level ◽  
Human Breast ◽  
Small Interference Rna ◽  
Breast Invasive Ductal Carcinomas

The transcription factor Pit-1/Pou1f1 regulates GH and prolactin (PRL) secretion in the pituitary gland. Pit-1 expression and GH regulation by Pit-1 have also been demonstrated in mammary gland. However, no data are available on the role of Pit-1 on breast PRL. To evaluate this role, several human breast cancer cell lines were transfected with either the Pit-1 expression vector or a Pit-1 small interference RNA construct, followed by PRL mRNA and protein evaluation. In addition, transient transfection of MCF-7 cells by a reporter construct containing the proximal PRL promoter, and ChIP assays were performed. Our data indicate that Pit-1 regulates mammary PRL at transcriptional level by binding to the proximal PRL promoter. We also found that Pit-1 raises cyclin D1 expression before increasing PRL levels, suggesting a PRL-independent effect of Pit-1 on cell proliferation. By using immunohistochemistry, we found a significant correlation between Pit-1 and PRL expression in 94 human breast invasive ductal carcinomas. Considering the possible role of PRL in breast cancer disorders, the function of Pit-1 in breast should be the focus of further research.

Gene Expression Analysis of Bexarotene Differentiated Acute Myeloid Leukemias Identifies Known and Novel Gene Targets.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1199-1199
Author(s):  
Patricia Vanessa Sanchez ◽  
Reid P Bissonnette ◽  
Donald E Tsai ◽  
Martin Carroll
Keyword(s):  
Transcription Factor ◽  
Retinoic Acid ◽  
Cell Differentiation ◽  
Cell Lines ◽  
Leukemic Cell ◽  
Myeloid Differentiation ◽  
Induced Differentiation ◽  
Pparγ Agonist ◽  
Acute Myeloid

Abstract Despite advances in understanding the molecular pathogenesis of acute myeloid leukemia (AML), therapy for relapsed disease remains inadequate with high mortalities. Clinicians at the University of Pennsylvania have demonstrated that the FDA approved retinoid X receptor (RXR) agonist bexarotene (Targretin™) stimulates leukemic cell differentiation in a subset patents with relapsed AML leading to clinical responses. This underscores the importance of identifying the mechanism by which bexarotene induces differentiation in AML in order to enhance the efficacy of this therapeutic approach. To understand the role of bexarotene and RXR receptors in leukemic cell differentiation, we initially utilized a pharmacogenetic approach to study the effects of bexarotene on AML cell lines using combinations of bexarotene with other differentiation induction agents. These studies demonstrate that bexarotene induces myeloid differentiation in MOLM14, HL60, THP-1, and NB4 cell lines but not in the myeloblastic cell line KG1a. Combination treatment of AML cell lines with bexarotene in combination with all trans retinoic acid (ATRA) enhanced differentiation suggesting that the mechanism of action for bexarotene is through RARα (retinoic acid receptor)/RXRα heterodimer stimulation. Consistent with this, differentiation induced by the drug combination was effectively blocked by the RAR antagonist, LG100815 and partially blocked by the RXR antagonist, LG101208. In contrast, bexarotene does not cooperate with valproic acid, theophylline, the PPARγ agonist rosiglitazone, or the LXR agonist T0901317. Preliminary data from quantitative RT-PCR and Affymetrix microarray analysis of bexarotene responsive AML cell lines at 3, 6, 12, and 96 hours post treatment has identified a subset of genes potentially regulated by bexarotene. CEBPε, a transcription factor known to play a critical role in granulopoiesis and PIM-1, a known oncogenic transcription factor, were among the genes that were significantly upregulated after bexarotene treatment of AML cells. Analysis of the functional role of C/EBPε in retinoid induced differentiation will be presented. Overall, this data supports the hypothesis that bexarotene, like ATRA, induces myeloid differentiation through activation of a RAR/RXR heterodimeric partner. However, other data suggests the presence of RAR independent pathways of signaling. LG100268, a pure RXR agonist induced myeloid differentiaton although not as robustly as bexarotene. Analysis of RAR and RXR mRNA expression in AML cell lines demonstrates that bexarotene does not induce expression of RARβ or p21, known targets induced by ATRA during myeloid differentiation. Chromatin immunoprecipitation assays demonstrate RXRα occupancy at RARβ and p21 promoter regions containing retinoid response elements (RARE). However, expression of these genes does not correlate with bexarotene-induced differentiation. This data suggests that although their expression has been linked to ATRA responsiveness, induction of RARβ and p21 expression is not necessary for retinoid induced myeloid differentiation. In summary, bexarotene induces myeloid differentiation through RAR dependent and independent pathways. Further analysis of the signaling events necessary for induction of myeloid differentiation by bexarotene may allow for improved selection of patients with AML who will respond to bexarotene.

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