Cloning and characterization of the cDNA and gene for human epitheliasin

Previously, we reported cloning and characterization of the mouse gene, epi theliasin. In the present work we cloned the cDNA of the full-length human orthologue and characterized its gene including 2 kb of 5' flanking sequenc e. Analysis of epitheliasin gene expression in adult tissues shows that it is expressed as 3.4 kb and 2 kb transcripts. The major 3.4 kb transcript is observed in the following order: prostate > colon > small intestine > panc reas > kidney > lung > liver. Epitheliasin transcripts in fetal tissues are observed only in kidney and lung. In situ hybridization analysis of tissue s revealed that epitheliasin was preferentially expressed in epithelial cel ls. The gene consists of 14 exons and 13 introns based on comparison with i ts cDNA sequence. In the 5' flanking region, we identified two transcriptio n start sites and three CpG islands encompassing a number of potential regu latory elements including SP1, SREBP, GRE/PRE and ERE. The region upstream of the transcription sites lacks a TATA box but contains an initiator-like element as well as a downstream promoter-like element. In vitro experiments with lymph node carcinoma of prostate (LNCaP) cells revealed that the epit heliasin gene was induced by androgens and the induction was not blocked by cycloheximide indicating that the induction required no intermediate prote in factors. Immunoprecipitation analysis showed that androgens strongly inc reased epitheliasin protein levels.