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

A novel mRNA isoform encoding the cell surface metalloproteinase meprin bet a 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 beta ', has an extended 5 ' UTR as compared t o the meprin beta mRNA isoform expressed in normal kidney and intestinal ep ithelium. The work herein aimed to determine the molecular mechanisms for t he expression of meprin beta and beta ' in normal and cancer cells, respect ively. Analysis of the 5 ' end of the mouse meprin beta gene revealed that the unique sequences in the beta and beta ' mRNA isoforms are encoded by se parate exons that are alternately spliced, and transcribed from independent promoters. By contrast, the human meprin beta and beta ' mRNAs have identi cal sequences except for 87 additional bases in the 5 ' UTR sequence of bet a ', indicating that a single, mixed usage promoter directs expression of t he isoforms. The region upstream of the human meprin beta ' transcription s tart site contained elements with homology to the promoters of intestine-sp ecific genes, interspersed with AP-1 and PEA3 elements; the latter were ess ential to meprin beta ' promoter activity in cancer cells. Phorbol myristal acetate increased meprin beta ' mRNA levels in cultured human colon cancer cells, providing further evidence that AP-1/PEA3 sites are actively involv ed in meprin beta ' expression.