The expression of p53-induced protein with death domain (Pidd) and apoptosis in oral squamous cell carcinoma.
The Pidd (p53-induced protein with death domain) gene was shown to be induced by the tumour suppressor p53 and to mediate p53-dependent apoptosis in mouse and human cells, through interactions with components of both the mitochondrial and the death receptor signalling pathways. To study the role of Pidd in clinical tumours, we measured its expression by quantitative reverse transcription-PCR in microdissected oral squamous cell carcinomas (OSCC) with and without p53 mutation. Tumour cell apoptosis was assessed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. Tumour proliferation was assessed by immunohistochemical staining for the Ki-67 antigen. We found a wide range of Pidd expression among OSCC. Statistical analysis revealed an association between Pidd expression and apoptotic index (Mann-Whitney test, P<0.001), consistent with a role of Pidd in apoptosis in this tumour type. Furthermore, we showed a positive correlation between apoptotic index and proliferative index that has not been previously described for OSCC. There was no correlation between Pidd expression and the p53 mutation status of these tumours, suggesting that Pidd expression may be regulated by p53-independent mechanisms. Further characterisation of these molecular defects in the control of proliferation and apoptosis should help in developing treatments that target OSCC according to their biological properties.
Bradley
G
G
Faculty of Dentistry, University of Toronto, Toronto, ON, Canada. grace.bradley@dentistry.utoronto.ca
Tremblay
S
S
Irish
J
J
MacMillan
C
C
Baker
G
G
Gullane
P
P
Benchimol
S
S
D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division; D053418:Death Domain Receptor Signaling Adaptor Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D002352:Carrier Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; C485896:PIDD1 protein, human; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53