Downregulation of KAI1 mRNA in localised prostate cancer and its bony metastases does not correlate with p53 overexpression.
Recent data have proposed that transcription of the KAI1 metastasis suppressor gene is directly mediated by p53 and that loss of KAI1 expression in advanced prostate cancer is simply due to loss of p53 function after mutation. To investigate this possibility, we have examined KAI1 mRNA (by in situ hybridisation) and p53 protein expression (by immunohistochemistry) as an indicator of wildtype or mutant p53, in a series of 77 paraffin-embedded prostate tissue samples, including post-mortem normal prostates (2), benign prostatic hyperplasia (10), localised cancer (grades 4-6, 25; grades 7-9, 21) and prostate-derived bony metastases (19). Overall, we confirmed that expression of KAI1 mRNA decreased from normal tissue, through localised cancer to bony metastases (P=0.055, tending to significance), while levels of p53 staining significantly increased with cancer progression (P=0.046). These were consistent with the possibility that loss of p53 function might be responsible for loss of KAI1 mRNA. However, by close examination of KAI1 and p53 in adjacent tissue sections, we found no correlation between decreased levels of KAI1 mRNA and overexpression of p53 protein (P=0.497). In addition, high levels of KAI1 mRNA could be identified in samples irrespective of p53 staining. Our data suggest that mutation of p53 is independent of the loss of KAI1 mRNA, and do not support a role for p53 in regulating the expression of KAI1.
Jackson
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Oncology Research Centre, Prince of Wales Hospital, Randwick, NSW, Australia. paul.jackson@unsw.edu.au
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Yardley
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Delprado
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Quinn
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D000328:Adult; D015703:Antigens, CD; D000954:Antigens, Surface; D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D015536:Down-Regulation; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051861:Kangai-1 Protein; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000494:pharmacology; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis
D015703:Antigens, CD; D000954:Antigens, Surface; C497688:CD82 protein, human; D004273:DNA, Neoplasm; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger