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Mutant p53 elicits context-dependent pro-tumorigenic phenotypes (ChIP-Seq)

ABSTRACT: These studies characterized R273C-p53 and R273H-p53 in prostate cancer cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE157335 | GEO | 2021/12/23

REPOSITORIES: GEO

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Mutant p53 elicits context-dependent pro-tumorigenic phenotypes (microarray)

Project description:These studies characterized R273C-p53 and R273H-p53 in prostate cancer cells

2021-12-23 | GSE157336 | GEO

Mutant p53 elicits context-dependent pro-tumorigenic phenotypes.

Project description:The tumor suppressor gene TP53 is the most frequently mutated gene in numerous cancer types, including prostate cancer (PCa). Specifically, missense mutations in TP53 are selectively enriched in PCa, and cluster to particular "hot spots" in the p53 DNA binding domain with mutation at the R273 residue occurring most frequently. While this residue is similarly mutated to R273C-p53 or R273H-p53 in all cancer types examined, in PCa selective enrichment of R273C-p53 is observed. Importantly, examination of clinical datasets indicated that TP53 heterozygosity can either be maintained or loss of heterozygosity (LOH) occurs. Thus, to mimic tumor-associated mutant p53, R273C-p53 and R273H-p53 isogenic PCa models were developed in the presence or absence of wild-type p53. In the absence of wild-type p53, both R273C-p53 and R273H-p53 exhibited similar loss of DNA binding, transcriptional profiles, and loss of canonical tumor suppressor functions associated with wild-type p53. In the presence of wild-type p53 expression, both R273C-p53 and R273H-p53 supported canonical p53 target gene expression yet elicited distinct cistromic and transcriptional profiles when compared to each other. Moreover, heterozygous modeling of R273C-p53 or R273H-p53 expression resulted in distinct phenotypic outcomes in vitro and in vivo. Thus, mutant p53 acts in a context-dependent manner to elicit pro-tumorigenic transcriptional profiles, providing critical insight into mutant p53-mediated prostate cancer progression.

| S-EPMC8755525 | biostudies-literature

Mutant p53 elicits context-dependent pro-tumorigenic phenotypes

Project description:Mutant p53 elicits context-dependent pro-tumorigenic phenotypes

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Mutant p53 elicits context-dependent pro-tumorigenic phenotypes

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-12-23 | GSE157337 | GEO

Mutant p53 elicits context-dependent pro-tumorigenic phenotypes (microarray)

Project description:Mutant p53 elicits context-dependent pro-tumorigenic phenotypes (microarray)

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Mutant p53 elicits context-dependent pro-tumorigenic phenotypes (ChIP-Seq)

Project description:Mutant p53 elicits context-dependent pro-tumorigenic phenotypes (ChIP-Seq)

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RNA-seq of cell lines containing p53-R273H or p53-R273H 22/23

Project description:RNA-seq of cell lines containing p53-R273H or p53-R273H 22/23

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RNA-seq of H1299 cells stably transfected with empty vector or the p53 mutant R273H.

Project description:This experiment aimed to determine the genes that were upregulated when mutant p53 (R273H) was expressed. We used H1299 lung cancer cells that are endogenously p53-null and overexpressed the p53 mutant.

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Genome-wide profiling of mutant p53 unveils a subset of lncRNAs correlated with colorectal cancer stemness maintenance [ChIP-seq]

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Genome-wide profiling of mutant p53 unveils a subset of lncRNAs correlated with colorectal cancer stemness maintenance [RNA-seq]

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