Relationship between expression of KAI1 metastasis suppressor gene, mRNA levels and p53 in human bladder and prostate cancer cell lines

Jackson, Paul; Grimm, Marc‐Oliver; Kingsley, Elizabeth A.; Brosius, Ute; Antalis, Toni M.; Yardley, Gina; Russell, Pamela J.

doi:10.1016/s1078-1439(01)00175-2

Cited by 24 publications

(31 citation statements)

References 23 publications

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“…In the PCa cell lines, p53 mutation status has been described previously (PC3, mutant-type p53; LNCaP, wild-type p53; DU145, mutant-type p53). (33) Because DNA hypermethylation of RIZ1 was detected in PC3 cells, mutation of the p53 gene may be induced by inactivation of RIZ1. In contrast, DNA hypermethylation of RIZ1 was not detected in DU145 cells despite the presence of p53 mutation.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer

et al. 2006

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The retinoblastoma protein-interacting zinc finger gene, RIZ1, is thought to be a tumor suppressor gene. RIZ1 is inactivated by mutation, deletion and DNA methylation in several human cancers. In the present study, the relationship between DNA methylation of RIZ1 and mutation of p53 was investigated in prostate cancer (PCa). In total, 47 cases of node-negative PCa (stages I-III) were analyzed. DNA methylation of the RIZ1 gene was detected in 20 (42.6%) of the 47 PCa tissues by methylation-specific polymerase chain reaction. DNA methylation of the RIZ1 gene was not associated with clinicopathological features. DNA methylation of RIZ1 tended to be present more frequently in PCa specimens with a high Gleason score (16/30, 53.3%) than in those with a low Gleason score (4/17, 23.5%); however, this tendency was not statistically significant (P = 0.0675). Nuclear accumulation of p53 was observed in four (8.5%) of 47 PCa specimens by immunostaining. All four PCa specimens with nuclear accumulation of p53 were stage III disease and showed DNA methylation of RIZ1. However, of the remaining 43 cancers without nuclear accumulation of p53, DNA methylation of RIZ1 was observed in only 16 (37.2%) specimens (P = 0.0272). Of the three PCa cell lines, only the PC3 cell line showed loss of RIZ1 mRNA due to DNA methylation, and this loss was rectified by treatment with a demethylating agent, 5-Aza-2′ ′ ′ ′-deoxycytidine. These results suggest that transcriptional inactivation of RIZ1 by aberrant DNA methylation may contribute to prostate carcinogenesis. Genetic alterations are likely associated with epigenetic alterations in PCa. (Cancer Sci 2007; 98: 32-36) P rostate cancer (PCa) is one of the most common cancers and the second leading cause of cancer death in men in the USA.(1) An understanding of the genetic and epigenetic pathways involved in the pathogenesis of PCa is essential for development of improved diagnostic and treatment modalities. A variety of genetic and epigenetic alterations are associated with PCa. (2,3) Epigenetic changes, such as DNA methylation of CpG islands, are detected commonly in human cancers. Hypermethylation of CpG islands is associated with silencing of many genes, especially defective tumor-related genes, and has been proposed as an alternative way to inactivate tumor-related genes in human cancers.(4,5) Identification of methylated genes may be useful in the diagnosis and treatment of PCa and may provide insight into prostate carcinogenesis. Prior studies have shown that DNA hypermethylation is a crucial mechanism in transcriptional silencing of tumor-related genes in PCa. (6,7) The retinoblastoma protein-interacting zinc finger gene, RIZ1, was isolated with a functional screen for retinoblastoma (Rb)-binding proteins.(8) Domain analysis suggested that RIZ1 is a histone methyltransferase (HMT) specific for the lysine 9 residue of histone H3, an activity known to be linked with transcriptional repression.(9) RIZ1 is considered to be a tumor suppressor gene because it can induce G 2 -M arrest and apo...

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Section: Discussionmentioning

confidence: 99%

DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer

et al. 2006

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“…Growth conditions for bladder cancer cell lines BL13, BL28, BL17/0/x1, BL17/2 and sublines, BL17/5, T24, RT112, J82, 5637 and the SV40-transformed urothelial cell line SV-HUC1 have been described previously (11). All lines were maintained in RPMI-1640 medium containing 10% FBS and 50 U/ml P/S.…”

Section: Methodsmentioning

confidence: 99%

Expression of KITENIN, a KAI1/CD82 binding protein and metastasis enhancer, in bladder cancer cell lines: Relationship to KAI1/CD82 levels and invasive behaviour

Rowe

Jackson²

2006

Oncol Rep

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Abstract. KITENIN is a newly identified binding partner of the KAI1/CD82 metastasis suppressor. Recent studies using a mouse model of colon cancer, have suggested that KITENIN might be a metastasis enhancer whose functions are modulated by an interaction with KAI1/CD82. To begin exploration of the possible importance of KITENIN to human cancer, we examined KITENIN mRNA (by RT-PCR) and protein expression (by Western blotting) in a large series of bladder cancer cell lines, and then compared these levels to the expression of KAI1/CD82 and of previously determined in vitro invasive behaviour of these same cancer cell lines. We report that KITENIN was uniformly expressed in all cancer cell lines, but those lines in which KAI1/CD82 was not detected, had a higher in vitro invasive ability and altered actin organisation (as determined by fluorescence microscopy), than those lines in which KAI1/CD82 was present. Our data suggest that the relationship between KITENIN and KAI1/CD82 may be an important determinant of tumour cell behaviour.

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“…While we cannot rule out a possibility that the PAbl 801 antibody used in the present study might not recognise all forms of mutant p53 protein, resulting in an underestimation of the proportion of tumour cells with mutant p53, and we acknowledge that specific p53 mutants within individual tumour cells were not identified, our conclusions are consistent with results of several recent studies, using different approaches, all of which have failed to find any supporting evidence for a direct relationship between p53 and KAI1. [30][31][32] Of particular relevance to this study, we have shown that there is no relationship between the presence of transcriptionally active wild-type p53 or specific transcriptionally inactive mutant p53 proteins and KAI1 levels, in a large series of prostate and bladder cancer cell lines. 30 Furthermore, transfection of cells with wild-type or mutant p53, the use of inducible p53 systems, the use of p53 inhibitors and agents that induce a p53-dependent response 31,32 have all been unable to demonstrate evidence for a p53-dependent induction of KAI1 mRNA.…”

Section: Discussionmentioning

confidence: 69%

“…[30][31][32] Of particular relevance to this study, we have shown that there is no relationship between the presence of transcriptionally active wild-type p53 or specific transcriptionally inactive mutant p53 proteins and KAI1 levels, in a large series of prostate and bladder cancer cell lines. 30 Furthermore, transfection of cells with wild-type or mutant p53, the use of inducible p53 systems, the use of p53 inhibitors and agents that induce a p53-dependent response 31,32 have all been unable to demonstrate evidence for a p53-dependent induction of KAI1 mRNA. Clearly, the KAI1 promoter contains a motif with homology to the consensus p53 binding motif, 24 but this does not necessarily imply that the KAI1 gene is a target for regulation by p53.…”

Section: Discussionmentioning

confidence: 69%

Downregulation of KAI1 mRNA in localised prostate cancer and its bony metastases does not correlate with p53 overexpression

Jackson

Yardley

et al. 2003

Prostate Cancer Prostatic Dis

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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 ¼ 0.055, tending to significance), while levels of p53 staining significantly increased with cancer progression (P ¼ 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 ¼ 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.

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Relationship between expression of KAI1 metastasis suppressor gene, mRNA levels and p53 in human bladder and prostate cancer cell lines

Cited by 24 publications

References 23 publications

DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer

DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer

Expression of KITENIN, a KAI1/CD82 binding protein and metastasis enhancer, in bladder cancer cell lines: Relationship to KAI1/CD82 levels and invasive behaviour

Downregulation of KAI1 mRNA in localised prostate cancer and its bony metastases does not correlate with p53 overexpression

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