scholarly journals FOXA1 defines cancer cell specificity

2016 ◽  
Vol 2 (3) ◽  
pp. e1501473 ◽  
Author(s):  
Gaihua Zhang ◽  
Yongbing Zhao ◽  
Yi Liu ◽  
Li-Pin Kao ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Target Genes ◽  
Human Cancer ◽  
Cell Types ◽  
Human Cancer Cell Lines ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Pioneer Transcription Factor ◽  
Specific Regulation

A transcription factor functions differentially and/or identically in multiple cell types. However, the mechanism for cell-specific regulation of a transcription factor remains to be elucidated. We address how a single transcription factor, forkhead box protein A1 (FOXA1), forms cell-specific genomic signatures and differentially regulates gene expression in four human cancer cell lines (HepG2, LNCaP, MCF7, and T47D). FOXA1 is a pioneer transcription factor in organogenesis and cancer progression. Genomewide mapping of FOXA1 by chromatin immunoprecipitation sequencing annotates that target genes associated with FOXA1 binding are mostly common to these cancer cells. However, most of the functional FOXA1 target genes are specific to each cancer cell type. Further investigations using CRISPR-Cas9 genome editing technology indicate that cell-specific FOXA1 regulation is attributable to unique FOXA1 binding, genetic variations, and/or potential epigenetic regulation. Thus, FOXA1 controls the specificity of cancer cell types. We raise a “flower-blooming” hypothesis for cell-specific transcriptional regulation based on these observations.

scholarly journals The Cytotoxic Activity of Diterpenoids from Isodon species

2012 ◽  
Vol 7 (8) ◽  
pp. 1934578X1200700
Author(s):  
Ayumi Ohsaki ◽  
Masaaki Ozawa ◽  
Kanki Komiyama ◽  
Akio Kishida ◽  
Takahiko Isobe
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cell Types ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines

Fifteen Isodon diterpenoids (1–15) were evaluated for their cytotoxic activity against HeLa and HL-60 human cancer cell lines, and against murine vincristine (VCR)-resistant P388 cells. Kamebanin (14) showed efficient cytotoxic activity against HeLa and HL-60 cells. In addition, although dihydroenmein (2) and trichorabdal B (7) were inactive against several tested cell types, they were found to have cytotoxic-enhancing activity of VCR against VCR-resistant P388 cells.

scholarly journals Circuits Regulating Superoxide and Nitric Oxide Production and Neutralization in Different Cell Types: Expression of Participating Genes and Changes Induced by Ionizing Radiation

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 701 ◽  
Author(s):  
Patryk Bil ◽  
Sylwia Ciesielska ◽  
Roman Jaksik ◽  
Joanna Rzeszowska-Wolny
Keyword(s):  
Nitric Oxide ◽  
Ionizing Radiation ◽  
Cancer Cell ◽  
Superoxide Radical ◽  
Human Cancer ◽  
Cell Types ◽  
Superoxide Radicals ◽  
No Production ◽  
Specific Expression ◽  
Human Cancer Cell Lines

Superoxide radicals, together with nitric oxide (NO), determine the oxidative status of cells, which use different pathways to control their levels in response to stressing conditions. Using gene expression data available in the Cancer Cell Line Encyclopedia and microarray results, we compared the expression of genes engaged in pathways controlling reactive oxygen species and NO production, neutralization, and changes in response to the exposure of cells to ionizing radiation (IR) in human cancer cell lines originating from different tissues. The expression of NADPH oxidases and NO synthases that participate in superoxide radical and NO production was low in all cell types. Superoxide dismutase, glutathione peroxidase, thioredoxin, and peroxiredoxins participating in radical neutralization showed high expression in nearly all cell types. Some enzymes that may indirectly influence superoxide radical and NO levels showed tissue-specific expression and differences in response to IR. Using fluorescence microscopy and specific dyes, we followed the levels and the distribution of superoxide and NO radicals in living melanoma cells at different times after exposure to IR. Directly after irradiation, we observed an increase of superoxide radicals and NO coexistent in the same subcellular locations, suggesting a switch of NO synthase to the production of superoxide radicals.

scholarly journals Suppression of the Oncogenic Transcription Factor FOXM1 by Proteasome Inhibitors

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Andrei L. Gartel
Keyword(s):  
Transcription Factor ◽  
Tumor Growth ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Proteasome Inhibitors ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Oncogenic Transcription Factor

The oncogenic transcription factor FOXM1 is one of the key regulators of tumorigenesis. We found that FOXM1 upregulates its own transcription and its protein stability depends on its interaction with the chaperone nucleophosmin. We also determined that FOXM1 is negatively regulated by the tumor suppressor p53. We identified the thiazole antibiotics Siomycin A and thiostrepton as inhibitors of transcriptional activity and FOXM1 expression via proteasome inhibition. In addition, we found that all tested proteasome inhibitors target FOXM1. We showed synergy between thiostrepton and bortezomib in different human cancer cell lines andin vivo.We generated isogenic human cancer cell lines of different origin with wild-type p53 or p53 knockdown and we demonstrated that proteasome inhibitors induce p53-independent apoptosis in these cells. Using RNA-interference or proteasome inhibitors to inhibit FOXM1 we found that suppression of FOXM1 sensitized human cancer cells to apoptosis induced by DNA-damaging agents or oxidative stress. We encapsulated thiostrepton into micelle-nanoparticles and after injection we detected accumulation of nanoparticles in tumors and in the livers of treated mice. This treatment led to inhibition of human xenograft tumor growth in nude mice. Our data indicate that targeting FOXM1 increases apoptosis and inhibits tumor growth.

scholarly journals p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality?

2020 ◽  
Vol 21 (4) ◽  
pp. 1346
Author(s):  
Chao Wang ◽  
Cui Rong Teo ◽  
Kanaga Sabapathy
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Target Genes ◽  
Growth Promotion ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Cellular Growth ◽  
Developmental Defects ◽  
Human Cancer Cell Lines ◽  
Cellular Survival

Identification of p73 as a structural homolog of p53 fueled early studies aimed at determining if it was capable of performing p53-like functions. This led to a conundrum as p73 was discovered to be hardly mutated in cancers, and yet, TAp73, the full-length form, was found capable of performing p53-like functions, including transactivation of many p53 target genes in cancer cell lines. Generation of mice lacking p73/TAp73 revealed a plethora of developmental defects, with very limited spontaneous tumors arising only at a later stage. Concurrently, novel TAp73 target genes involved in cellular growth promotion that are not regulated by p53 were identified, mooting the possibility that TAp73 may have diametrically opposite functions to p53 in tumorigenesis. We have therefore comprehensively evaluated the TAp73 target genes identified and validated in human cancer cell lines, to examine their contextual relevance. Data from focused studies aimed at appraising if p53 targets are also regulated by TAp73—often by TAp73 overexpression in cell lines with non-functional p53—were affirmative. However, genome-wide and phenotype-based studies led to the identification of TAp73-regulated genes involved in cellular survival and thus, tumor promotion. Our analyses therefore suggest that TAp73 may not necessarily be p53’s natural substitute in enforcing tumor suppression. It has likely evolved to perform unique functions in regulating developmental processes and promoting cellular growth through entirely different sets of target genes that are not common to, and cannot be substituted by p53. The p53-related targets initially reported to be regulated by TAp73 may therefore represent an experimental possibility rather than the reality.

scholarly journals Co-expression of glutaminase K and L isoenzymes in human tumour cells

2005 ◽  
Vol 386 (3) ◽  
pp. 535-542 ◽  
Author(s):  
Cristina PÉREZ-GÓMEZ ◽  
José A. CAMPOS-SANDOVAL ◽  
Francisco J. ALONSO ◽  
Juan A. SEGURA ◽  
Elisa MANZANARES ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Human Cancer ◽  
Fold Increase ◽  
Cell Types ◽  
Tumour Cells ◽  
Human Tumour ◽  
Human Cancer Cell Lines ◽  
Human Tumour Cells ◽  
Frequent Event ◽  
Glutaminase Activity

The pattern of expression of glutaminase isoenzymes in tumour cells has been investigated to clarify its role in the malignant transformation and the prospect of its use as a clinically relevant factor. Using leukaemia cells from medullar blood of human patients and several established human cancer cell lines, we have developed a competitive RT (reverse transcriptase)-PCR assay to quantify simultaneously K-type (kidney-type) and L-type (liver-type) glutaminase mRNAs. Co-expression of both transcripts and higher amounts of L-type mRNA were always found in all cancer cell types analysed. However, mature lymphocytes from the medullar blood of a patient suffering aplasia did not express the K-type transcript and showed a 15-fold increase of L-type transcript. Co-expression was also confirmed at the protein level using isoform-specific antibodies; nevertheless, it did not correlate with the relative abundance of glutaminase transcripts and strong K-type protein signals were detected. On the other hand, marked differences were found with regard to glutamate inhibition and phosphate activation of tumour glutaminase activity. Taken together, the protein data suggest that K isoform would account for the majority of glutaminase activity in these human tumour cells. The results confirm that simultaneous expression of both isoenzymes in human cancer cells is a more frequent event than previously thought. Furthermore, the present work and other previous data suggest that K isoform is up-regulated with increased rates of proliferation, whereas prevalence of the L isoform seems to be related with resting or quiescent cell states.

scholarly journals Regulation of Transcription Factor NF-κB in Its Natural Habitat: The Nucleus

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 753
Author(s):  
Susanne Bacher ◽  
Johanna Meier-Soelch ◽  
Michael Kracht ◽  
M. Lienhard Schmitz
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Natural Habitat ◽  
Transcriptional Response ◽  
Gene Clusters ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Specific Cell ◽  
Regulation Of Transcription ◽  
Specific Regulation

Activation of the transcription factor NF-κB elicits an individually tailored transcriptional response in order to meet the particular requirements of specific cell types, tissues, or organs. Control of the induction kinetics, amplitude, and termination of gene expression involves multiple layers of NF-κB regulation in the nucleus. Here we discuss some recent advances in our understanding of the mutual relations between NF-κB and chromatin regulators also in the context of different levels of genome organization. Changes in the 3D folding of the genome, as they occur during senescence or in cancer cells, can causally contribute to sustained increases in NF-κB activity. We also highlight the participation of NF-κB in the formation of hierarchically organized super enhancers, which enable the coordinated expression of co-regulated sets of NF-κB target genes. The identification of mechanisms allowing the specific regulation of NF-κB target gene clusters could potentially enable targeted therapeutic interventions, allowing selective interference with subsets of the NF-κB response without a complete inactivation of this key signaling system.

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