Deregulation of p73 isoform equilibrium in benign prostate hyperplasia and prostate cancer.
p73, a p53 homologue important for growth suppression, differentiation and induction of apoptosis, utilizes different promoters and undergoes alternative splicing to produce several isoforms differing in their ability to overlap p53 functions. Using reverse transcriptase-polymerase chain reaction (RT-PCR) to assess the mRNA levels of p53, p73 (total and isoforms specific for exons 2 and 13), MDM2, CDKN1A and beta2-microglobulin as internal control, we analyzed 35 prostate carcinomas and 44 benign prostate hyperplasias (BPH) compared to 14 normal prostates. Shift of p73 isoform mRNA levels from exon 13 lacking to exon 13 containing copies was observed in 80% of prostate cancer cases and in 52.3% of BPH specimens, and from exon 2 containing to exon 2 lacking (p73Deltaexon2) transcripts in 45.7% of cancer cases, but only in 9.1% of BPH samples. From these findings we deduce that p73 isoform balance is disrupted in prostate cancer and BPH, suggesting that this disequilibrium could play an important role in both prostate hyperplasia and malignancy.
Arvanitis
Demetrios A
DA
Laboratory of Clinical Virology, Medical School, University of Crete, PO Box 2208, Heraklion 71003, Crete, Greece.
Lianos
Emmanouel
E
Soulitzis
Nikolaos
N
Delakas
Demetrios
D
Spandidos
Demetrios A
DA
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D001613:beta 2-Microglobulin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2