A FOLLISTATIN-LIKE GENE, MAC25, MAY ACT AS A GROWTH SUPPRESSOR OF OSTEOSARCOMA CELLS

mac25, a retinoic acid-inducible gene that is expressed at high levels in senescent epithelial cells, was initially cloned as a gene that is differentially expressed in meningioma, Although the homology of its product with members of family of insulin-like growth factor-binding p roteins was suggested, the product also exhibits strong homology to fo llistatin, an activin-binding protein, However, a domain corresponding to the carboxyl terminus of follistatin is not found in mac25, The ca rboxyl-terminally truncated form of follistatin, generated by alternat ive splicing, has stronger activin-binding activity than the complete form, This result suggests that mac25 might act as an activated follis tatin, Clonal growth of a p53-deficient osteosarcoma cell line was str ongly inhibited when the murine mac25 gene, as well as the p53 gene, w as introduced, Resembling activins that belong to the transforming gro wth factor-beta (TGF-beta) superfamily, mac25 and p53 might associate with similar but distinct targets, namely cyclin-dependent kinase inhi bitors. However, there is no evidence for compensation of p53 function by mac25 in the development of p53-deficient mice, as judged from the pattern of expression of mac25 in mice, mac25 might act as a tumor su ppressor, modulating signaling of the TGF-beta family, as does alpha-i nhibin.