Expression of the activated p185erbB2 tyrosine kinase in human epithelial cells leads to MAP kinase activation but does not confer oncogenicity

Exp Cell Res. 1997 Mar 15;231(2):251-9. doi: 10.1006/excr.1996.3468.

Abstract

Amplification of the c-erbB2 gene and overexpression of p185erbB2 is found in approximately one-third of primary breast and ovarian cancers and also in some colon carcinomas. Moreover, a single point mutation in erbB2(V 664 E) confers transforming potential to erbB2 in NIH3T3 cells, even when expressed at low levels. To examine the transformation potential of erbB2 or erbB2(V-E) in colon epithelial cells, we have transfected a nontumorigenic clone of SW 613-S cells with either wild-type p185erbB2 or mutated p185erbB2(V-E). In contrast to p185erbB2, p185erbB2(V-E) associated constitutively with members of the Shc protein family, leading to phosphorylation of Shc and to stimulation of mitogen-activated protein kinase (MAP kinase). However, constitutive activation of MAP kinase activation in p185erbB2(V-E) expressing cells did not result in a tumorigenic phenotype. In addition, p185erbB2(V-E) expressing cells displayed a reduced ability to grow in soft agar compared to the parental cell line. In contrast these transfected cells were able to grow in three-dimensional collagen gels, whereas parental cells were not. Thus, expression of erbB2(V-E) in SW 613-S cells induced multiple changes in intracellular signaling and in growth requirement phenotype, particularly in response to the extracellular environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport*
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / pathology
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Transformation, Neoplastic
  • Collagen
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / pathology
  • Enzyme Activation
  • Enzyme Induction / drug effects
  • Epidermal Growth Factor / pharmacology
  • Epithelial Cells
  • Epithelium / enzymology
  • Female
  • Gels
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / enzymology*
  • Intestinal Mucosa / pathology
  • Mice
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Neoplasm Transplantation
  • Oncogenes
  • Phosphorylation
  • Point Mutation
  • Protein Processing, Post-Translational
  • Proteins / metabolism
  • Receptor, ErbB-2 / biosynthesis*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / physiology
  • Recombinant Fusion Proteins / physiology
  • Shc Signaling Adaptor Proteins
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Gels
  • Neoplasm Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • SHC1 protein, human
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Epidermal Growth Factor
  • Collagen
  • Receptor, ErbB-2
  • Calcium-Calmodulin-Dependent Protein Kinases