FREQUENT INACTIVATION OF PTEN IN PROSTATE-CANCER CELL-LINES AND XENOGRAFTS

Loss of chromosome 10q is a frequently observed genetic defect in pros tate cancer. Recently, the PTEN/MMAC1 tumor suppressor gene was identi fied and mapped to chromosome 10q23.3. We studied PTEN structure and e xpression in 4 in vitro cell lines and 11 in vivo xenografts derived f rom six primary and nine metastatic human prostate cancers. DNA sample s were allelotyped for eight polymorphic markers within and surroundin g the PTEN gene. Additionally, the nine PTEN exons were tested for del etions. In five samples (PC3, PC133, PCEW, PC295, and PC324), homozygo us deletions of the PTEN gene or parts of the gene were detected. PC29 5 contained a small homozygous deletion encompassing PTEN exon 5. In t wo DNAs (PC82 and PC346), nonsense mutations were found, and in two (L NCaP and PC374), frame-shift mutations were found. Missense mutations were not detected. PTEN mRNA expression was clearly observed in all ce ll lines and xenografts without large homozygous deletions, showing th at PTEN down-regulation is not an important mechanism of PTEN inactiva tion. The high frequency (60%) of PTEN mutations and deletions indicat es a significant role of this tumor suppressor gene in the pathogenesi s of prostate cancer.