A GROWTH FACTOR-INDUCIBLE GENE ENCODES A NOVEL NUCLEAR-PROTEIN WITH ZINC-FINGER STRUCTURE

Growth factors rapidly induce numerous genes that encode regulatory proteins, many of which have been identified by cDNA cloning. In this study, differential hybridization was used to screen a cDNA library constructed from human mammary carcinoma MDA-468 cells that were stimulated with transforming growth factor beta-1 (TGF-beta1) in the presence of cycloheximide. One of the cDNA clones that was induced by TGF-beta1 was found to have a nucleotide sequence that predicts a 9,450-Da protein with homology to regulatory DNA-binding proteins. This clone was designated metallopan-stimulin-1 (MPS-1) because it encodes a metalloprotein whose mRNA is expressed in a wide variety of actively proliferating cells and tumor tissues. MPS-1 protein contains one ''zinc finger'' domain of the C4 type, similar to those present in proteins of the steroid/thyroid hormone receptor superfamily and other DNA-binding proteins. The mRNA for MPS-1 was induced in MDA-468 cells by fetal calf serum, TGF-beta1, TGF-beta2, and cAMP analogues. The MPS-1 gene is expressed at relatively high levels in several human carcinoma cell lines, particularly those derived from ectodermal layers, and at higher levels in melanomas (ontogenically of neural origin). In contrast, the MPS-1 mRNA is expressed at low levels in normal WI-38 human lung diploid fibroblasts in culture. We hypothesize that MPS-1 protein may play a role as a potentially important mediator of cellular proliferative responses to various growth factors and other environmental signals.