Localization, expression and genomic structure of the gene encoding the human serine protease testisin

Testisin is a recently identified human serine protease expressed by premei otic testicular germ cells and is a candidate tumor suppressor for testicul ar cancer. Here, we report the characterization of the gene encoding testis in, designated PRSS21, and its localization on the short arm of human chrom osome 16 (16p13.3) between the microsatellite marker D16S246 and the radiat ion hybrid breakpoint CY23HA. We have further refined the localization to c osmid 406D6 in this interval and have established that the gene is approxim ately 4.5 kb in length, and contains six exons and five intervening introns . The structure of PRSS21 is very similar to the human prostasin gene (PRSS 8) which maps nearby on 16p11.2, suggesting that these genes may have evolv ed through gene duplication. Sequence analysis showed that the two known is oforms of testisin are generated by alternative pre-mRNA splicing. A major transcription initiation site was identified 97 nucleotides upstream of the testisin translation start and conforms to a consensus initiator element. The region surrounding the transcription initiation site lacks a TATA conse nsus sequence, but contains a CCAAT sequence and includes a CpG island. The 5'-flanking region contains several consensus response elements including Sp1, AP1 and several testis-specific elements. Analysis of testisin gene ex pression in tumor cell lines shows that testisin is not expressed in testic ular tumor cells but is aberrantly expressed in some tumor cell lines of no n-testis origin. These data provide the basis for identifying potential gen etic alterations of PRSS21 that may underlie both testicular abnormalities and tumorigenesis. (C) 2000 Elsevier Science B.V. All rights reserved.