p53 increases experimental metastatic capacity of murine carcinoma cells.

Abstract

Transfection of a cloned p53 gene into a murine bladder carcinoma cell with a low metastatic capacity led to elevated levels of p53 protein in clonal transfectants. After intravenous inoculation into syngeneic mice, p53-transfected clones showed significantly increased metastatic potential in comparison with control transfectants. The observed change did not seem to be due to a change in growth potential per se since the cell lines showed similar growth properties in vitro.

Roles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress

“…Dominant gainof-function mutations in p53 have been shown to increase oncogenic transformation when expressed in p53-null cells (Wolf et al, 1984), and to participate in tumor progression (Dittmer et al, 1993;Iwamoto et al, 1996;Pohl et al, 1988). A speci®c class of dominant p53 mutations has now been identi®ed in cells from Li-Fraumeni Syndrome patients which speci®cally interferes with the mitotic spindle checkpoint and promotes genomic instability (Gualberto et al, 1998).…”

Radioresistant MTp53-expressing rat embryo cell transformants exhibit increased DNA-dsb rejoining during exposure to ionizing radiation

“…Furthermore, there is evidence in the literature to suggest that MTp53 proteins may mediate their cellular e ect(s) in a manner independent of their interaction with WTp53 proteins (i.e. so-called`gain of function'), based on altered the ability of certain MTp53 proteins to alter cell proliferation, tumourigenicity, metastatic ability and show novel interactions with nuclear-matrix associated proteins, when over-expressed in null-p53 cell lines (Dittmer et al, 1993;Muller et al, 1996;Pohl et al, 1988;Shaulsky et al, 1991).…”

Changes in p53 expression can modify cell shape of ras-transformed fibroblasts and epitheliocytes

“…The former is evidently due to the ability of mutant protein to bind the product of the wild-type (wt) p53 gene alleles and to form heteromeric complexes showing decreased capacity to interact with p53-responsive elements (reviewed in Milner, 1994;Prives, 1994). The latter activities can be revealed upon transduction of mutant p53 alleles into the p53-null cells and include the ability to increase clonogenicity in semisolid medium in vitro (Dittmer et al, 1993) as well as to enhance tumorigenicity (Shaulsky et al, 1991;Dittmer et al, 1993) and metastatic capacity or invasiveness in vivo (Pohl et al, 1988;Hsiao et al, 1994).…”