A novel mRNA isoform (meprin b H ) of the cell-surface protease subunit meprin b was previously identified in human colon cancer cells. The study reported here revealed that this mRNA isoform was identical within the protein coding region and at the 3 H end to the b isoform of normal intestine but that it contained an extended 5 H untranslated region. Meprin b H mRNA was expressed in the human breast cancer cell lines MCF-7 and SK-BR-3, in the human osteosarcoma cell line U2 Os, and in the human pancreatic cancer cell line BxPC-3. Meprin b mRNA, but not b H mRNA, was expressed in human fetal kidney cells. We cloned and sequenced genomic DNA encoding portions of the promoter region of the meprin b gene. The unique sequences present in the b H mRNA were present in the human genomic DNA immediately upstream of the transcription start site for the b mRNA. The human meprin promoter sequence was searched for potential transcription-factor binding sites, and putative activator protein-1, polyoma enhancer activator 3 (PEA3), CCAAT enhancer-binding protein beta, and estrogen-receptor binding sites were identified along with binding sites for the intestine-specific cdx-2 transcription factor. The activity of meprin promoter/luciferase reporter gene constructs transfected into U2 Os cells was highest with constructs containing 83 and 639 bp of promoter DNA. These regions of the promoter each contain a putative PEA3 element. Treatment of the human colon adenocarcinoma cell line HT29-18C 1 with 50 or 100 ng/mL phorbol myristal acetate for 8 h increased meprin b H mRNA levels. Likewise, U2 Os cells transfected with the -639/luciferase or -1800/luciferase constructs showed a phorbol myristal acetate±inducible increase in reporter gene activity, indicating that the PEA3 element within the -639 construct or other elements further upstream respond to phorbol ester.