Dissociation of cellular transformation from platelet-derived growth factor independence

Abstract

ST2-3T3, a spontaneously transformed BALB/c-3T3 cell line which does not require platelet-derived growth factor (PDGF) for growth, was fused to THO2, a PDGF-responsive non-transformed BALB/c-3T3 cell line, in order to learn whether transformation is expressed coordinately with PDGF independence. Hybrid cells were selected and grown in medium containing both HAT (hypoxanthine-aminopterin-thymidine) and ouabain; unfused cells of each parental type were killed in HAT-ouabain medium. Five independently isolated ST2-3T3xTHO2 hybrid cell lines were established and characterized for both transformation and PDGF responsiveness. All five were transformed, having a disorganized growth pattern and achieving a final cell density similar to that of ST2-3T3 cells. Two of these lines did not respond to a brief treatment with PDGF: the mitogen neither induced the synthesis of a PDGF-modulated lysosomal protein (termed MEP), nor stimulated the cells to enter the S phase; one line responded to PDGF by synthesizing both MEP and DNA, whereas two others synthesized MEP but not DNA. In contrast, four independently isolated cell lines obtained by fusing PDGF-responsive non-transformed BALB/c-3TC cells to the THO2 line were all PDGF-responsive for both MEP and DNA synthesis and were not transformed. It appears that PDGF independence is not required for the transformation of BALB/c-3T3 cells.