Expression of PTEN in malignant and non-malignant human prostate tissues: comparison with p27 protein expression.
The role of the putative tumour suppressor PTEN in prostate carcinogenesis is controversial. There are conflicting data regarding the rate of its gene inactivation, the role of transcriptional and post-transcriptional factors, as well as its relationship to tumour progression and to the potential downstream regulator, the cell-cycle inhibitor p27. The present study has assessed the in situ expression of PTEN mRNA and protein in 26 prostate intraepithelial neoplasias (PINs), 58 primary prostate carcinomas, and 15 metastases. Although there was a correlation between PTEN mRNA and protein expression, mRNA detection exceeded detection of protein in 19% of PINs and 30% of all invasive tumours. Using RT-PCR and western blotting on microdissected tissue, this discrepancy was attributed, at least in part, to transcription of the PTEN pseudo-gene, which lacks introns. Total or partial loss of PTEN protein occurred with tumour progression but this association was not statistically significant. Analysing the relationship between PTEN and p27 protein expression on consecutive sections by immunohistochemistry, the results do not support a direct link between the two oncosuppressors, other than an associated loss of expression in advanced tumour stages. However, in the basal cells of prostate glands and in most PINs, an inverse relationship was observed between PTEN and p27. This may reflect the existence of a functional balance that controls the cell cycle in prostatic epithelium and that is probably disturbed in invasive tumour cells.
Fenic
Irina
I
Institute of Pathology, University of Giessen, Langhans Strasse 10, 35385 Giessen, Germany.
Franke
Folker
F
Failing
Klaus
K
Steger
Klaus
K
Woenckhaus
Joachim
J
D000230:Adenocarcinoma / Q000235:genetics; D000918:Antibody Specificity / Q000235:genetics; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis*; D009124:Muscle Proteins; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis / Q000235:genetics*; D011467:Prostate / Q000502:physiology* / Q000503:physiopathology; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D014176:Protein Biosynthesis; D011544:Pseudogenes / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics*
D008840:Microfilament Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C058992:Tagln protein, mouse; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human