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Transin is a transformation-associated gene which is expressed constitutively in rat fibroblasts transformed by a variety of oncogenes and in malignant mouse skin carcinomas but not benign papillomas or normal skin. It has been demonstrated that, in nontransformed Rat-1 cells, transin RNA expression is modulated positively by epidermal growth factor (EGF) and negatively by transforming growth factor beta (TGF-beta); other peptide growth factors were found to have no effect on transin expression. Results presented here indicate that both protein synthesis and continuous occupancy of the EGF receptor by EGF were required for sustained induction of transin RNA. Treatment with TGF-beta inhibited the ability of EGF to induce transin, whether assayed at the transcriptional level by nuclear run-on analysis or at the level of transin RNA accumulation by Northern (RNA) blot analysis of cellular RNA. TGF-beta both blocked initial induction of transin transcription by EGF and halted established production of transin transcripts during prolonged treatment. These results suggest that TGF-beta acts at the transcriptional level to antagonize EGF-mediated induction of transin gene expression.

Friend spleen focus-forming virus shuts down its gene expression frequently (ca. 10(-3) per generation) in a cis-dominant hereditable fashion in various murine cells but much less frequently in rat cells (less than 10(-6) per generation). Thus, nonexpresser variants were isolated at high frequency from murine cell lines by immunoselection directed against virus-encoded cell surface glycoproteins and also simply by subcloning cells from lines which had been cultured for many generations. Studies of independently infected cell clones indicate that shutdown is a property of the cell line rather than of the specific proviral site. Nucleic acid blot analyses suggest that shutdown correlates with decreased transcription. Moreover, preliminary evidence indicates that other murine retroviruses also shut down frequently in murine but not in rat cells and that shutdown of replication-competent murine leukemia viruses with accompanying loss in interference to superinfection may be the rate-limiting reaction enabling cells to acquire multiple proviruses in their chromosomes. High-frequency shutdown in vivo would have important pathological consequences.