A retrovirus vector expressing the putative mammary oncogene int-1 causes partial transformation of a mammary epithelial cell line

• Published in: Cell Vol. 46; no. 7; pp. 1001 - 1009
• Main Authors: Brown, Anthony M.C., Wildin, Robert S., Prendergast, Thomas J., Varmus, Harold E.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 26.09.1986; Cell Press
• Subjects: Animals; Applied sciences; Cell Adhesion; Cell Cycle; Cell Line; Cell Transformation, Neoplastic - genetics; DNA Replication; Exact sciences and technology; Gene Expression Regulation; Genetic Vectors; Hydrogen-Ion Concentration; Leukemia Virus, Murine; Mammary Neoplasms, Experimental - genetics; Mice; Other techniques and industries; Proto-Oncogenes
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(86)90699-9

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.