Viral Ha-ras mediated mammary tumor progression

An immortal mammary epithelial cell line, Comma 1D, and primary cultures of mammary epithelial cells were used to examine the effects of vHa-ras on mammary tumor development. In culture, Comma 1D and primary cells were morphologically indistinguishable. Infection with a replication defective vHa-ras retroviral vector (psi ras) did not alter their in vitro phenotype. Uninfected Comma 1D cells implanted into gland-cleared mammary fat pads gave rise to dysplastic outgrowths, while implants of primary cells gave rise to normal gland structures. After psi ras infection, implants of Comma 1D cells progressed to adenocarcinomas and those of primary cells resulted in initiated dysplastic outgrowths. High level infection of either cell type with replication competent HaMSV (psi ras plus helper virus) resulted in in vitro transformation and undifferentiated in vivo tumors. Thus, in vivo analysis was necessary to detect the observed correlation between tumorigenic stage and level of infection. In this system, expression of vHa-ras was vital but not sufficient for mammary tumor initiation and progression, which resulted from an accumulation of events that did not need to occur in a specific order.