The int-2 gene product acts as an epithelial growth factor in transgenic mice

EMBO J. 1990 Mar;9(3):907-13. doi: 10.1002/j.1460-2075.1990.tb08188.x.

Abstract

The induction of mammary tumors by mouse mammary tumor virus (MMTV) is thought to occur through proviral activation of one or more cellular genes. One of these, int-2, encodes a 27 kd protein which exhibits striking homology to the basic fibroblast growth factor family. To assess directly the role of the int-2 protein in cell proliferation, we have established transgenic mice which carry the int-2 gene driven by the MMTV promoter/enhancer. Expression of the int-2 gene in female transgenic mice results in pronounced mammary gland hyperplasia. Interestingly, expression of the MMTV-int-2 transgene in the prostate gland of male carriers results in a benign, but dramatic, epithelial hyperplasia similar to benign prostatic hypertrophy (BPH), a common but poorly understood disorder in human populations. Together, these results indicate that the int-2 product can act as a potent growth factor in these epithelial tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA, Viral / genetics
  • Female
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factors*
  • Gene Expression*
  • Genetic Vectors
  • Growth Substances / genetics*
  • Male
  • Mammary Glands, Animal / microbiology
  • Mammary Glands, Animal / pathology
  • Mammary Tumor Virus, Mouse / genetics*
  • Mammary Tumor Virus, Mouse / isolation & purification
  • Mice
  • Mice, Transgenic
  • Prostate / microbiology
  • Prostate / pathology
  • Prostatic Hyperplasia / microbiology
  • Prostatic Hyperplasia / pathology
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology
  • Restriction Mapping

Substances

  • DNA, Viral
  • Fgf3 protein, mouse
  • Fibroblast Growth Factor 3
  • Growth Substances
  • Proto-Oncogene Proteins
  • Fibroblast Growth Factors