Meprin B: Transcriptional and posttranscriptional regulation of the meprin β metalloproteinase subunit in human and mouse cancer cells

A novel mRNA isoform encoding the cell surface metalloproteinase meprin β is expressed in mouse teratocarcinoma cells and in a variety of cultured human cancer cells. In both mouse and human cells, the cancer cell‐specific mRNA isoform, referred to as β', has an extended 5′ UTR as compared to the meprin β mRNA isoform expressed in normal kidney and intestinal epithelium. The work herein aimed to determine the molecular mechanisms for the expression of meprin β and β' in normal and cancer cells, respectively. Analysis of the 5′ end of the mouse meprin β gene revealed that the unique sequences in the β and β' mRNA isoforms are encoded by separate exons that are alternately spliced, and transcribed from independent promoters. By contrast, the human meprin β and β' mRNAs have identical sequences except for 87 additional bases in the 5′ UTR sequence of β', indicating that a single, mixed usage promoter directs expression of the isoforms. The region upstream of the human meprin β' transcription start site contained elements with homology to the promoters of intestine‐specific genes, interspersed with AP‐1 and PEA3 elements; the latter were essential to meprin β' promoter activity in cancer cells. Phorbol myristal acetate increased meprin β' mRNA levels in cultured human colon cancer cells, providing further evidence that AP‐1/PEA3 sites are actively involved in meprin β' expression.