Induction of two alternatively spliced evi-1 proto-oncogene transcripts by cAMP in kidney cells.
The evi-1 proto-oncogene is normally predominantly expressed in the kidney. We report here that evi-1 transcripts are also abundant in foetal kidney and expression is retained in primary kidney cell cultures. However available kidney cell lines express low or no evi-1 mRNA. In the human renal cell carcinoma cell line, A704, evi-1 is inducible approximately 16-fold by elevating intra-cellular cAMP levels with either forskolin or dibutyryl cAMP. TPA down-regulates evi-1 mRNA production and blocks forskolin mediated induction. Similar effects are seen in NIH3T3 cells and primary kidney cell cultures. Induction of evi-1 gene expression by forskolin does not alter the ratio of full length and an alternatively spliced transcript which encodes a protein lacking two repeats of the zinc finger motif. Potential regulation of evi-1 expression in kidney by hormones which modulate intra-cellular cAMP levels suggest that it can respond to environmental cues which might be important to the normal physiological role of this protein in kidney differentiation, development and function.
Bartholomew
C
C
Beatson Institute for Cancer Research, Cancer Research Campaign Beatson Laboratories, Bearsden, Glasgow.
Clark
A M
AM
D016475:3T3 Cells; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D007668:Kidney / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C499305:Mecom protein, mouse; D009838:Oligodeoxyribonucleotides; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D014157:Transcription Factors; D000242:Cyclic AMP