Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome.

By Gene A. Lang, T. Iwakuma, Young-Ah Suh, Geng-Hung Liu, Vasundhara Rao, J. Parant, Y. Valentin-Vega, Tamara Terzian, L. Caldwell, Louise C. Strong and 2 more. Cell, 2004

1,099 citations recorded by the source corpus.

Subfields: Biotechnology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/7076085d5a760b2fa6bfdd2216dd47cccb7d7b13

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Citations in the corpus

Hepatocellular carcinoma pathogenesis: from genes to environment (2006, background): “As noted above, the inactivation of p53 through mutation or viral oncoprotein sequestration is a common event in HCC, and p53 knock-in alleles containing dominant point mutations have been shown to cause genomic instability in mouse model”
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”
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).”
Mutant p53 gain-of-function in cancer. (2010, background): “…in parallel in 2004, showed that when compared with p53 knockout animals, mice carrying mutp53 alleles tended to develop more aggressive, metastatic tumors, as well as a higher frequency of tumor types that are associated with p53 mutations in human cancer (Lang et al. 2004; Olive et al. 2004).”
Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer (2010, background): “These data are consistent with a broader literature in which mutant p53 has been suggested to play an important role in metastasis beyond that of knockout p53; however, these studies have generally yielded quite subtle increases in metastasis (11, 12, 40).”
Mutant p53 in Cancer: New Functions and Therapeutic Opportunities (2014, background): “…V173L, Y234C, R248W REFb stable/transient Smith et al., 1999 C174Y Saos-2 stable/transient Preuss et al., 2000 R172H (human R175H) MEF endogenous Lang et al., 2004 R175H SK-BR3 endogenous Bossi et al., 2006 C194T T47D endogenous Nguyen et al., 2013; Vikhanskaya et al., 2007 A220G Huh-7…”
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).”
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”
Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers. (2015, background): “This clinical gradient of germline TP53 mutations had already been suggested by mouse models of LFS, which had revealed the phenotypic severity of dominant-negative mutations, as compared with null mutations.(29-34) Interestingly, in pedigrees including childhood ACC, we detected, as previously repo”
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, background): “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).”
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 ubiquitination: Mdm2 and beyond. (2006, background): “Recent studies of mouse models that harbor hotspot p53 missense mutations reveal that high levels of the mutant p53 proteins do indeed accumulate in the tumor cells of these animals (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).”