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.