INDUCTION OF 2 ALTERNATIVELY SPLICED EVI-1 PROTOONCOGENE TRANSCRIPTS BY CAMP IN KIDNEY-CELLS

The evi-1 proto-oncogene is normally predominantly expressed in the ki dney. We report here that evi-1 transcripts are also abundant in foeta l kidney and expression is retained in primary kidney cell cultures. H owever available kidney cell lines express low or no evi-1 mRNA. In th e human renal cell carcinoma cell line, A704, evi-1 is inducible appro ximately 16-fold by elevating intra-cellular cAMP levels with either f orskolin or dibutyryl cAMP. TPA down-regulates evi-1 mRNA production a nd blocks forskolin mediated induction. Similar effects are seen in NI H3T3 cells and primary kidney cell cultures. Induction of evi-1 gene e xpression by forskolin does not alter the ratio of full length and an alternatively spliced transcript which encodes a protein lacking two r epeats of the zinc finger motif. Potential regulation of evi-1 express ion in kidney by hormones which modulate intra-cellular cAMP levels su ggest that h can respond to environmental cues which might be importan t to the normal physiological role of this protein in kidney different iation, development and function.