Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome.

By K. Olive, D. Tuveson, Zachary C Ruhe, Bob Yin, Nicholas A. Willis, R. Bronson, D. Crowley, T. Jacks. Cell, 2004

1,348 citations recorded by the source corpus.

Subfields: Biotechnology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/e2061d502e80d0df56f2deabd992447a0f24fda9

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Citations in the corpus

Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. (2007, background): “We crossed mice heterozygous for a clinically relevant hot spot mutation (p53 R172H ; Olive et al., 2004) with Hsf1 +/À mice.”
Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis. (2011, background): “Moreover, p53+/R172H and p53+/ R270H mice developed allele-specific tumor spectra, distinct from that of p53+/– mice.(81,100,101) On one hand, when examining mice homozygous to R172H, it cannot be concluded that the mutant form has an additional GOF over p53 knockout since p53R172H/R172H and p53–/– ”
Mutant p53 Disrupts Mammary Acinar Morphogenesis via the Mevalonate Pathway (2012, positive): “In vivo knockin mice harboring two tumorderived mutants of p53 (equivalent to R175H and R273H in humans) display an altered tumor spectrum as well as more metastatic tumors when compared to p53 null mice (Lang et al., 2004; Olive et al., 2004).”
Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer (2010, methodology): “These mice develop a distinct spectrum of tumors compared with those arising in p53 heterozygous null mice, with an increased incidence of osteosarcomasandcarcinomas (11, 12).”
p53 and metabolism (2009, background): “Many tumour-derived mutants of p53 are highly penetrant oncogenes, rather than simply mutants with loss of wild-type p53 function”
Targeting p53 pathways: mechanisms, structures and advances in therapy (2023, background): “250,251 In mouse models of pancreatic cancer that speci ﬁ cally express oncogenic KRAS and mutant TP53 , more than twice as many metastatic lesions were observed as in TP53 knockout mice.”
TP53 mutations in human cancers: origins, consequences, and clinical use. (2010, background): “Knockin mice with R175H and R273H mutants (Lang et al. 2004; Olive et al. 2004) showed increased metastases and different cancer distribution compared with p53 knockout mice, providing in vivo evidence of GOF.”
p53 in health and disease (2007, result): “Many studies have indicated that the consequences of expressing these mutant forms of p53 are not equivalent to the simple loss of p53, and this is most clearly seen in mouse models in which expression of mutant p53 is strongly linked to a change in tumour spectrum and an increase in metastatic pote”
Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. (2005, methodology): “…with germline transmission of the Trp53R172H allele, for example, normal tissues retain the wild-type allele, and Trp53 is not detected immunohistochemically; however, in the tumors that developed in these animals with demonstrated LOH, Trp53 expression was readily detectable (Olive et al., 2004).”
Mutant p53: one name, many proteins. (2012, background): “Remarkably, both knockin mutations produce an altered tumor spectrum in addition to more metastatic tumors (Liu et al. 2000; Lang et al. 2004; Olive et al. 2004).”
TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes (2007, background): “Studies in mouse models of LFS have reported evidence of GOF for R175H and R273H mutants (Lang et al., 2004; Olive et al., 2004).”
Regulating the p53 pathway: in vitro hypotheses, in vivo veritas (2006, result): “These results again agree with data from mouse models: targeted mutations R172H and R270H in the mouse (corresponding to the R175H and R273H mutations common in human tumours) dramatically affected mouse p53 functions, and acquired oncogenic properties that promoted metastasi”
When mutants gain new powers: news from the mutant p53 field (2009, background): “However, recent in vivo data challenge this hypothesis by demonstrating that mutant Trp53 knock-in mice ( Trp53 encodes mouse p53) do not accumulate mutant p53 in normal tissue”
A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. (2009, neutral): “Why do tumor cells retain a disabled tumor suppressor, rather than losing it for good? An important step in answering this question has been the generation of mutant-p53 knockin mice (Lang et al., 2004; Olive et al., 2004).”
Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database (2007, background): “Studies in mouse models of LFS have reported evidence of GOF for R175H and R273H mutants [Lang et al., 2004; Olive et al., 2004].”
Mutant p53 drives invasion by promoting integrin recycling. (2009, methodology): “These results are consistent with studies showing a similar role for mutant p53 in xenograft studies (Adorno et al., 2009) and in mice expressing mutant p53 in all tissues (Lang et al., 2004; Olive et al., 2004).”