Messenger RNA stabilization accounts for elevated basic fibroblast growth factor transcript levels in a human astrocytoma cell line.
Basic fibroblast growth factor (bFGF) is a potent autocrine and paracrine mitogen for cells of mesodermal origin. Although the protein is present in substantial amounts in a variety of tissues, the level of mRNA is undetectable in most normal tissues. This has led to speculation that bFGF mRNA is very unstable, but the half-life of this mRNA has not been described. A number of mRNAs encoding growth factors and growth-related proteins are known to be short-lived and posttranscriptionally regulated. In the present study we have examined the half-life of bFGF mRNA in two human tumor cell lines, which contain high (U87-MG) and low (T98-G) steady state bFGF mRNA levels. The half-life of bFGF mRNA, determined after transcriptional arrest with actinomycin-D, was approximately 10 min in T98-G cells, but was extended to 120 min in the presence of cycloheximide. In contrast, bFGF transcripts in U87-MG cells were very stable with a half-life considerably greater than 5 h. This was not attributable to a general stabilization of mRNA in the U87-MG line, since the half-life of c-myc mRNA in the two cell lines was similar (10 and 15 min in T98-G and U87-MG, respectively). Cycloheximide had no effect on the steady state level of bFGF in U87-MG cells. These findings suggest that posttranscriptional processes play an important role in the regulation of bFGF transcript levels and demonstrate that loss of posttranscriptional regulation could contribute to elevated bFGF expression in some tumors.
Murphy
P R
PR
Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Guo
J Z
JZ
Friesen
H G
HG
D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D003513:Cycloheximide / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006207:Half-Life; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D003513:Cycloheximide