Elevated expression of c-myc proto-oncogene in scleroderma fibroblasts.
Scleroderma is a connective tissue disease characterized by the overproduction of extracellular matrix components. The mechanisms of fibrosis may involve increased fibroblast proliferation in the scleroderma lesion due to the presence of cells with abnormal growth properties, in addition to the well-known over-production of several matrix components. The c-myc proto-oncogene has been implicated in dysregulation of cell growth in neoplastic cells and as an essential element of the response to growth factors in normal cells. Therefore, to investigate the molecular basis of growth in scleroderma, we compared expression of c-myc gene in scleroderma and control cells. In this report, we show that under low serum conditions (1% serum), scleroderma fibroblasts express 2.5-3 higher level of c-myc message. Moreover, stimulation of c-myc after addition of fresh 10% serum is blunted in scleroderma compared to control cells. Observed c-myc expression in scleroderma is similar to c-myc expression in transformed cells. In addition, there is also increased proliferation of scleroderma cells in 1% serum as measured directly by a nuclear label assay. These data suggest the presence of fibroblasts with abnormal growth properties in the scleroderma lesion.
Trojanowska
M
M
Department of Medicine, Medical University of South Carolina, Charleston 29425.
Wu
L T
LT
LeRoy
E C
EC
D015139:Blotting, Southern; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D009693:Nucleic Acid Hybridization; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012595:Scleroderma, Systemic / Q000235:genetics*; D012867:Skin / Q000378:metabolism; D014158:Transcription, Genetic
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases