Frequent inactivation of PTEN in prostate cancer cell lines and xenografts.
Loss of chromosome 10q is a frequently observed genetic defect in prostate cancer. Recently, the PTEN/MMAC1 tumor suppressor gene was identified and mapped to chromosome 10q23.3. We studied PTEN structure and expression in 4 in vitro cell lines and 11 in vivo xenografts derived from six primary and nine metastatic human prostate cancers. DNA samples were allelotyped for eight polymorphic markers within and surrounding the PTEN gene. Additionally, the nine PTEN exons were tested for deletions. In five samples (PC3, PC133, PCEW, PC295, and PC324), homozygous deletions of the PTEN gene or parts of the gene were detected. PC295 contained a small homozygous deletion encompassing PTEN exon 5. In two DNAs (PC82 and PC346), nonsense mutations were found, and in two (LNCaP and PC374), frame-shift mutations were found. Missense mutations were not detected. PTEN mRNA expression was clearly observed in all cell lines and xenografts without large homozygous deletions, showing that PTEN down-regulation is not an important mechanism of PTEN inactivation. The high frequency (60%) of PTEN mutations and deletions indicates a significant role of this tumor suppressor gene in the pathogenesis of prostate cancer.
Vlietstra
R J
RJ
Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
van Alewijk
D C
DC
Hermans
K G
KG
van Steenbrugge
G J
GJ
Trapman
J
J
D000818:Animals; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D016368:Frameshift Mutation; D017353:Gene Deletion; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D011471:Prostatic Neoplasms / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D005819:Genetic Markers; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human