A retrovirus vector expressing the putative mammary oncogene int-1 causes partial transformation of a mammary epithelial cell line.
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.
D000818:Animals; D002448:Cell Adhesion; D002453:Cell Cycle; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004261:DNA Replication; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006863:Hydrogen-Ion Concentration; D009052:Leukemia Virus, Murine; D008325:Mammary Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D011519:Proto-Oncogenes