MUTATION AND EXPRESSION ANALYSIS OF THE PUTATIVE PROSTATE TUMOR-SUPPRESSOR GENE PTEN

The chromosomal region 10q23-24 is frequently deleted in a number of t umour types, including prostate adenocarcinoma and glioma. A candidate tumour-suppressor gene at 10q23.3, designated PTEN or MMAC1, with put ative actin-binding and tyrosine phosphatase domains has recently been described. Mutations in PTEN have been identified in cell lines deriv ed from gliomas, melanomas and prostate tumours and from a number of t umour specimens derived from glial, breast, endometrial and kidney tis sue. Germline mutations in PTEN appear to be responsible for Cowden di sease. We identified five PTEN mutations in 37 primary prostatic tumou rs analysed and found that 70% of tumours showed loss or alteration of at least one PTEN allele, supporting the evidence for PTEN involvemen t in prostate tumour progression, We raised antisera to a peptide from PTEN and showed that reactivity occurs in numerous small cytoplasmic organelles and that the protein is commonly expressed in a variety of cell types. Northern blot analysis revealed multiple RNA species; some arise as a result of alternative polyadenylation sites, but others ma y be due to alternative splicing.