Regulation of the c-fms promoter in murine tumour cell lines

P Favot, X Yue, D A Hume

Research output: Contribution to journalArticlepeer-review

Abstract

Macrophage colony-stimulating factor (CSF-1) mRNA was detected in a wide range of murine tumour cell lines. Stable transfection with a CSF-1 receptor (c-fms) expression plasmid increased the number and size of colonies formed in soft agar by tumour cell lines that were already clonogenic, but did not induce transformation in non-clonogenic lines. To identify mechanisms that might lead to ectopic expression of c-fms, the regulation of the exon 2 promoter of the gene, which flanks the transcription start sites in macrophages, was examined. In transient and stable transfections this promoter was as active in non-macrophage tumour cell lines as it was in RAW264 macrophages. Promoter activity in non-macrophage lines was serum-dependent and was activated further in lines stably transfected with c-fms. Cis-acting elements required for serum-dependent activity lay outside the 300 bp proximal promoter that was sufficient for maximal activity in RAW264 macrophages, but the c-fms-responsive elements were retained in the proximal promoter. Exon 2 promoter activity was selectively suppressed in non-macrophage lines by inclusion of intron 2, which has been implicated in transcription attenuation. Lewis lung carcinoma cells were able to partly bypass this block and expressed c-fms mRNA when grown in limiting serum. The finding that c-fms promoter activity and c-fms mRNA levels are responsive to growth factor signalling pathways provides an insight into mechanisms that may lead to ectopic c-fms expression in tumour cells.
Original languageEnglish
Pages (from-to)1371-81
Number of pages11
JournalOncogene
Volume11
Issue number7
Publication statusPublished - 5 Oct 1995

Keywords

  • Animals
  • Base Sequence
  • Exons
  • Lung Neoplasms
  • Macrophage Colony-Stimulating Factor
  • Mice
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Receptor, Macrophage Colony-Stimulating Factor
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured

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