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 oncogenes (Ki-ras, mos, src, fms, fes, met, and trk), by a DNA tumor virus (SV40), or by a chemical carcinogen (N-nitrosomethylurea) were studied. In contrast to NIH-3T3 cells or simian virus 40 (SV40)-transformed 3T3 cells, all the other transformed NIH-3T3 cell lines expressed a 4.5 kb transforming growth factor-alpha (TGF alpha)-specific mRNA transcript and secreted immunoreactive and biologically active TGF alpha ranging from 100 to 225 ng/10(8) cells/48 h. In addition, in the transformed cell lines that were secreting elevated levels of biologically active TGF alpha, there was a 75-95% reduction in the total number of epidermal growth factor receptors on these cells. A 2.6 kb TGF beta mRNA transcript and TGF beta protein in the conditioned medium (30-140 ng/10(8) cells/48 h) was also detected in those lines expressing TGF alpha. Basic fibroblast growth factor-like activity (11-50 ng/10(8) 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.
Ciardiello
F
F
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Valverius
E M
EM
Colucci-D'Amato
G L
GL
Kim
N
N
Bassin
R H
RH
Salomon
D S
DS
D000818:Animals; D015152:Blotting, Northern; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002472:Cell Transformation, Viral / Q000235:genetics; D003470:Culture Media; D066246:ErbB Receptors / Q000096:biosynthesis; D005346:Fibroblast Growth Factors / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000096:biosynthesis*; D008770:Methylnitrosourea; D051379:Mice; D009857:Oncogenes / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D011061:Poly A / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D013539:Simian virus 40 / Q000502:physiology; D015291:Transforming Growth Factors / Q000096:biosynthesis
D003470:Culture Media; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011061:Poly A; D005346:Fibroblast Growth Factors; D008770:Methylnitrosourea; D015291:Transforming Growth Factors; D066246:ErbB Receptors