A Retrovirus Vector Expressing the Putative Mammary Oncogene int-1 Causes Partial Transformation of a Mammary Epithelial Cell Line

Cell. 1986 Sep 26;46(7):1001-9. doi: 10.1016/0092-8674(86)90699-9.

Abstract

In mammary tumors induced by the mouse mammary tumor virus (MMTV), the int-1 gene is frequently activated by adjacent proviral insertions and is thereby strongly implicated in tumorigenesis. To seek a direct biological effect of int-1 that would validate its proposed role as an oncogene, we constructed a retrovirus vector containing the gene and examined its effects on tissue culture cells. Expression of int-1 in a mammary epithelial cell line caused striking morphological changes, unrestricted growth at high cell density, and focus formation on a monolayer, although the cells were not tumorigenic in vivo. This partial transformation induced by int-1 was not observed in cells infected by an otherwise identical virus bearing a frameshift mutation in the gene. These findings strongly support the hypothesis that int-1 plays a functional role in MMTV-induced mammary tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Cycle
  • Cell Line
  • Cell Transformation, Neoplastic / genetics*
  • DNA Replication
  • Gene Expression Regulation
  • Genetic Vectors
  • Hydrogen-Ion Concentration
  • Leukemia Virus, Murine
  • Mammary Neoplasms, Experimental / genetics*
  • Mice
  • Proto-Oncogenes*