DIFFERENTIAL GROWTH-FACTOR EXPRESSION IN TRANSFORMED MOUSE NIH-3T3 CELLS

The expression of growth factor‐specific mRNA transcripts and the presence of biologically active growth factors in the conditioned medium and in the cell extracts from mouse NIH‐3T3 cells transformed by different oncogences (Ki‐ras, mos, src, fms, fes, met, and trk), by DNA tumor virus (SV40), or by a chemical carcinogen (N‐nitrosomethylurea) were studied. In contrast to NIH‐3T3 cells or simain virus 40 (SV40)‐transformed 3T3 cells, all the other transformed NIH‐3T3 cell lines express a 4.5 kb transforming growth factor‐α (TGFα)‐specific mRNA transcript and secreted immunoreactive and biologically active TGFα ranging from 100 to 225 ng/108 cell/48 h. In addition, in the transformed cell lines that were secreting elevated levels of biologically active TGFα, there was a 75–95% reduction in the total number of epidermal growth factor receptors on these cells. A 2.6 kb TGFβ mRNA transcript and TGFβ protein in the conditioned medium (30–140ng/108 cells/48h) was also detected in those lines expressing TGFα. Basic fibroblast growth factor‐like activity (11–50 ng/108 cells) was detected in the cell lysates from NIH‐3T3 cells transformed with N‐nitrosomethylurea or with trk, where expression of specific 6.9 and 3.9 kb mRNA transcripts for basic fibroblast growth factor could also be found. B chain (c‐sis) expression of platelet‐derived growth factor was present only in trk‐transformed NIH‐3T3 cells in which specific c‐sis 6.5 and 4.6 kb transcripts were identified. In contrast, platelet‐derived growth factor A chain expression of 2.9 and 2.3 kb transcripts was found in ras‐, met‐, mos‐, and fms‐transformed NIH‐3T3 cells. These results suggest that the expression of different sets of growth factors is controlled in part by structurally distinct groups of transforming genes. Copyright © 1990 Wiley‐Liss, Inc.