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

Oncogene
N GloushankovaB Kopnin

Abstract

p53 plays an important role in restriction of abnormal cell proliferation. Loss of this safeguard function induced by p53 mutations seems to be a key mechanism in oncogenesis. It cannot be excluded however, that in addition to elimination of p53-dependent checkpoints and/or apoptosis p53 mutations may cause additional effects that contribute to oncogenic transformation. In order to analyse the effects of wild-type (wt) and mutant p53 on expression of ras-induced morphological transformation we used the method of computer-assisted morphometry. The following parameters were determined: a) the area covered by the spread cells; b) dispersion and c) elongation of cell contours. The last two indices characterise cell shape. Elongation indicates the degree of bipolarity of cell contour and dispersion-the degree of its multipolarity. Transformation of Rat1 and mouse 10(3) fibroblasts by N-rasasp12 oncogene was accompanied by dramatic decrease of cell area and increase of dispersion and elongation. IAR-2 discoid epitheliocytes expressing exogenous ras oncogene transformed into polarised cells with decreased cell area. Fluorescent microscopic examination of actin cytoskeleton stained with rhodamine-phalloidin had shown that ras-induced t...Continue Reading

Citations

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