Murine gamma interferon inhibits v-mos-induced fibroblast transformation via down regulation of retroviral gene expression.
Expression of the retroviral vector Neor myeloproliferative sarcoma virus (MPSV), which contains the v-mos oncogene and the neomycin resistance gene, leads to neoplastic transformation of mouse fibroblasts. Murine recombinant gamma interferon (IFN-gamma) could revert the neoplastic properties of established Neor MPSV-transformed cell lines to an apparently untransformed phenotype. In the presence of IFN-gamma, the Neor MPSV transformants showed a greater than 97% reduction of cloning efficiency in soft agar, strongly reduced proliferative capacity, and morphological changes. The IFN-gamma-induced phenotypic reversion was preceded by a rapid and selective reduction of all retroviral RNA species, apparently due to IFN-gamma action on the long terminal repeat of Neor MPSV. The mRNA levels of cellular genes either remained unaffected (beta-actin) or were even enhanced (H-2) in IFN-gamma-treated Neor MPSV-transformed cells. Upon removal of IFN-gamma, retroviral gene expression was fully recovered and a gradual reappearance of the transformed phenotype of these cells within 3 weeks was noted. These data show that IFN-gamma can cause a virtually complete, but reversible, inhibition of v-mos-induced neoplastic properties in transformed fibroblasts by selective down regulation of retroviral RNA levels.
D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D009053:Sarcoma Viruses, Murine / Q000235:genetics*
D012333:RNA, Messenger; D007371:Interferon-gamma