Expression of neoplasia-related proteins of chemically transformed HuT fibroblasts in human osteosarcoma HOS fibroblasts and modulation of actin expression upon elevation of tumorigenic potential.

Two sets of abundant cytoplasmic transformation-specific polypeptides, p788/p789 and p219/p220, have been identified by comparing in vitro-transformed human fibroblasts with diploid human fibroblasts. These polypeptides are also expressed by the human fibrosarcoma and osteosarcoma cell lines HT1080 the human fibrosarcoma and osteosarcoma cell lines HT1080 and HOS, respectively. HOS cells, however, synthesize only one of the two electrophoretic forms of each marker set, p789 and p219, at greatly reduced rates compared to the rates of synthesis found for HT1080 cells and the in vitro-transformed cell lines. Induction of expression of these neoplastic marker polypeptides is independent of the activation of a transforming gene that will induce focus formation in confluent mouse 3T3 cell monolayers. Activation of the met oncogene in MNNG-HOS cells and simultaneous elevation of tumorigenic potential did not lead to a significant change in the rate of the 600 most abundant polypeptide species with the exception of one of the two cytoplasmic actin polypeptides. While the normal ratio of beta-to gamma-actin which is approximately 2:1 was expressed in "untransformed" HOS cells, MNNG-HOS cells synthesized 50% less beta-actin resulting in a 1:1 ratio of beta-actin to gamma-actin. Our finding here, together with our previous characterization of the human beta-actin gene, leads us to predict that one of two functional beta-actin genes expressed in HOS cells has been inactivated in MNNG-HOS cells by either a regulatory or structural gene mutation.