Mutation and expression analysis of the putative prostate tumour-suppressor gene PTEN.
The chromosomal region 10q23-24 is frequently deleted in a number of tumour types, including prostate adenocarcinoma and glioma. A candidate tumour-suppressor gene at 10q23.3, designated PTENor MMAC1, with putative actin-binding and tyrosine phosphatase domains has recently been described. Mutations in PTEN have been identified in cell lines derived from gliomas, melanomas and prostate tumours and from a number of tumour specimens derived from glial, breast, endometrial and kidney tissue. Germline mutations in PTEN appear to be responsible for Cowden disease. We identified five PTEN mutations in 37 primary prostatic tumours analysed and found that 70% of tumours showed loss or alteration of at least one PTEN allele, supporting the evidence for PTEN involvement 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 may be due to alternative splicing.
Gray
I C
IC
Imperial Cancer Research Technology, Applied Development Laboratory, St Bartholomew's Hospital, London, UK.
Stewart
L M
LM
Phillips
S M
SM
Hamilton
J A
JA
Gray
N E
NE
Watson
G J
GJ
Spurr
N K
NK
Snary
D
D
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012334:RNA, Neoplasm / Q000032:analysis; D025521:Tumor Suppressor Proteins
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human