PMID: 9543387Apr 16, 1998Paper

Rac1 and extracellularly regulated kinase activation are sufficient for E1A-dependent cooperative transformation of primary epithelial cells, but progression can only be modulated by E1A or Rac1

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
R S FischerM P Quinlan

Abstract

Ras transformation of fibroblast cell lines requires activation of multiple distinct signal pathways that act synergistically. E1A-ras cotransformation of primary epithelial cells is enhanced by distinct mutations in the second exon of E1A, resulting in "hypertransformation" and metastasis. The molecular and cellular differences in the in vitro properties of such transformed cells are characterized here. Hypertransformed cells grew faster and to higher saturation densities; had smaller, more refractile cell morphologies with pronounced actin microspikes; and were less adhesive when compared with wild-type (WT) E1A+ras-expressing cells. No significant differences were observed in extracellularly regulated kinase activity levels between the hypertransformed and WT transformed cells. Activated raf and Rac1 together were sufficient for transformation of primary epithelial cells with E1A, whereas neither alone was competent to cooperate with E1A. In the presence of activated ras and WT E1A, activated Rac1 expression effected all of the hypertransformation properties. Dominant-negative Rac1 expression was suppressive of the hypertransformation phenotype, including cell morphology, actin cytoskeletal structures, decreased growth rates...Continue Reading

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