SV40T-immortalized lung alveolar epithelial cells display post-transcriptional regulation of proliferation-related genes

To study the regulation of proliferation of lung alveolar epithelial type 2 cells, we have established a cell line derived from neonatal type 2 cells by transfection with the SV40 large T antigen gene. We find that this cell line, designated SV40-T2, displays the same post-transcriptional control of expression of proliferation-related genes, including c-myc, ornithine decarboxylase, thymidine kinase, and histone, that we have previously described in primary isolates of type 2 cells (Clement et al., Proc. Natl. Acad. Sci. USA 87, 318-322, 1990). Both proliferating and nonproliferating SV40-T2 cells express these genes at high levels, but their translation products are only detected in proliferating cells. Using the histone gene as an example, we have found that regulation of expression occurs at the level of transcription and of mRNA turnover, as previously described in other mammalian systems. However, in addition, regulation of expression also occurs at the level of translation of the histone mRNA, because its protein product is not detectable in nonproliferating SV40-T2 cells. We have analyzed the steps which are potentially involved in this translational regulation of histone gene expression in SV40-T2 cells. In both proliferating and nonproliferating cells, histone mRNA was found to be efficiently transported from the nucleus to the cytoplasm and to associate with the translationally active heavy polysomal fractions. These results indicate that control of histone gene expression (and perhaps that of other proliferation-related genes) in lung epithelial cells may involve either rapid and selective degradation of histone protein or binding factor(s) which modulate translational efficiency of histone mRNA.