Overexpression of the wild type p73 gene in human bladder cancer

Yokomizo, Akira; Mai, Ming; Tindall, Donald J.; Liu, Cheng; Bostwick, David G.; Naito, Seiji; Smith, Jeremy C.; Liu, Wanguo

doi:10.1038/sj.onc.1202474

Cited by 121 publications

(85 citation statements)

References 19 publications

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“…p73 mutations seem to be a very rare event. However, the expression of p73 has been shown to be higher in tumour tissue than in the corresponding normal tissue both at the mRNA level (Loiseau et al, 1999;Takada et al, 1999;Yokomizo et al, 1999) and at the protein level (Bjork-Eriksson et al, 1999;MacCallum and Hupp, 1999;Peters et al, 1999;Scherr, 1999;Tannapfel et al, 1999;Cai et al, 2000;Herath et al, 2000;Ng et al, 2000). The origin of such increased expression and its function in tumorigenesis is not known, but it could be involved in the triggering of this p73 immune response.…”

Section: Discussionmentioning

confidence: 99%

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

et al. 2001

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Summary p53 antibodies have been found in the sera of patients with various types of cancer. The presence of these antibodies is generally associated with p53 accumulation in the tumour that is believed to trigger this humoral response. The recent discovery of 2 new members of the p53 family, p73 and p63, led us to study the specificity of this immune response towards the 3 proteins. Serum samples from 148 patients with various types of cancer were tested for antibodies against p73 and p63 using immunoprecipitation. 72 patients were previously shown to have p53 antibodies whereas 76 were negative. The control group consisted of 50 blood donors. p73 were detected in 22/148 (14.9%) of the cancer patients (11/72 in the group with p53-antibodies and 11/76 in the negative group). Only two sera from the control (4%) were positive. p63 antibodies were detected in only 4/148 (2.7%) of the cancer patients. Epitope mappings were performed and demonstrate that p73 antibodies are directed toward the central region of the p73 protein whereas p53 antibodies react predominantly toward the amino-and the carboxy-terminus of p53. Our results indicate that there is a specific immune response toward the p73 protein in cancer patients, a finding supported by an increasing number of publications describing p73 accumulation in tumoral cells.

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Section: Discussionmentioning

confidence: 99%

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

et al. 2001

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“…Here we observed elevated protein expression and uncharacteristic localization of pinin protein within cells comprising a RCC tumor mass. Although it is generally assumed that tumor suppressors are negative regulators of tumor formation and are often down-regulated in cancer development, observations of over-expression of TS proteins such as pRb, p53, p73, p27, p16 in di erent tumors are not uncommon Doki et al, 1997;Kaur et al, 1998;Shapiro et al, 1995;Warneford et al, 1991;Yokomizo et al, 1999). The over-expression of a tumor suppressor may imply a compensatory mechanism which may function to circumvent the disrupted regulatory pathway of wild-type TS protein (Benedict et al, 1999;Emig et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the gene encoding pinin/DRS/memA and evidence for its potential tumor suppressor function

Shi

Ouyang²,

Sugrue

2000

Oncogene

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Several cell adhesion-related proteins have been shown to act as tumor-suppressors (TS) in the neoplastic progression of epithelial-derived tumors. Pinin/DRS/memA was ®rst identi®ed in our laboratory and it was shown to be a cell adhesion-related molecule. Our previous study demonstrated that restoration of pinin expression in transformed cells not only positively in¯uenced cellular adhesive properties but also reversed the transformed phenotype to more epithelial-like. Here, we show by FISH analysis that the gene locus for pinin is within 14q13. The alignment of the pinin gene with STS markers localized the gene to the previously identi®ed TS locus D14S75-D14S288. Northern analyses revealed diminished pinin mRNA in renal cell carcinomas (RCC) and certain cancer cell lines. Immunohistochemical examination of tumor samples demonstrated absent or greatly reduced pinin in transitional cell carcinoma (TCC) and RCC tumors. TCC-derived J82 cells as well as EcR-293 cells transfected with full-length pinin cDNA demonstrated inhibition of anchorage-independent growth of cells in soft agar. Furthermore, methylation analyses revealed that aberrant methylation of pinin CpG islands was correlated with decreased/absent pinin expression in a subset of tumor tissues. These data lend signi®cant support to the hypothesis that pinin/DRS/memA may act as a tumor suppressor in certain types of cancers.

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“…However, also in analogy to other hematological malignancies, rare deletions of p53 as well as p73 seem to be associated with advanced disease stages in MM. Since some studies have indicated that aberrant p73 gene expression levels might play a role in tumor growth or progression, 55 mutational as well as expression analyses of the p73 gene in MM samples are under way to elucidate a possible role of gene silencing and mutation in the pathogenesis of MM.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9][10][11][12] Mutations or deletions of genes encoding these proteins have rarely been found in human cancers or hematological malignancies so far. 8,[13][14][15][16][17][18][19][20][21] After being mapped to the chromosomal region 1p35-1p36, p73 has been postulated to act as a tumor suppressor gene, as this region was shown to be deleted in several human malignancies including neuroblastoma, pheochromocytoma, oligodendroglioma, melanoma, merkel cell cancer, germ cell cancer, breast cancer, ovarian cancer, liver cancer and colon cancer as well as in some precancerous lesions like colorectal adenomas. 20,[22][23][24][25][26] Recently published preliminary data discussed the role of p73 in hematologic neoplasias, 27,28 as well as in renal cell carcinoma 29 and lung cancer.…”

Section: Introductionmentioning

confidence: 99%

True

1999

Leukemia

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Recently, p73, a protein with structural and functional similarities to p53, an extensively studied tumor suppressor gene, has been cloned. After being mapped to the chromosomal region 1p35-1p36, it has been postulated to act as a tumor suppressor gene, too, as this region is altered in several human malignancies. Deletions of the short arm of chromosome 1 have frequently been described in multiple myeloma (MM) whereas structural abnormalities of the 17p13 region including p53 are rare events in this disease. Since it has been proposed that especially neoplasias lacking p53 alterations might show a loss of heterozygosity at 1p35-1p36, we studied the frequency of p53 and p73 deletions in bone marrow mononuclear cells of 68 patients with MM, two patients with monoclonal gammopathy of undetermined significance and four patients with plasma cell leukemia. Dual-color fluorescence in situ hybridization (FISH) for p53 and p73 was performed using commercially available DNA probes for 17p13.3 and the microsatellite marker D1Z2, respectively. Centromeric DNA probes served to distinguish gene deletions from whole chromosome losses. In contrast to recently published FISH results, we only detected heterozygous p53 deletions in eight out of the 74 patients, three of them showing a monosomy 17. Heterozygous deletions of the D1Z2 region at 1p36 were found in six cases with one patient having a monosomy 1. Neither homozygous deletions of either chromosomal region nor nullisomies 1 or 17 could be detected. These results argue against a major role of p73 deletions in MM. As MM patients with 1p structural abnormalities have a significantly poorer survival rate than those with normal karyotypes, the role of other putative tumor suppressor genes located at the chromosomal region 1p36 in the pathogenesis of MM has to be determined.

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Overexpression of the wild type p73 gene in human bladder cancer

Cited by 121 publications

References 19 publications

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

Characterization of the gene encoding pinin/DRS/memA and evidence for its potential tumor suppressor function

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