Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alterations of tumour suppressor genes are considered crucial steps in the development of human cancers. Expressions of p53 protein, a product of the tumour suppressor gene altered most commonly in human cancers examined so far, were investigated immunohistochemically in 18 osteosarcomas and 40 other malignant and benign lesions of bone. A monoclonal antibody clone PAb240, which recognizes a common conformational epitope of mutant p53 proteins, stained nuclei of tumour cells in 12 of 18 osteosarcomas (67%). Six tumours (33%) particularly showed positive immunoreactions in more than half of the tumour cells. PAb240 also stained tumour cells in a small number of other malignant bone tumours, such as malignant fibrous histiocytoma, chondrosarcoma, and Ewing's sarcomas. Furthermore, a small number of cells of giant-cell tumours were positively stained. In contrast, PAb240 was completely negative in 21 benign bone tumours and reactive lesions examined. Another monoclonal antibody clone PAb1801, which reacts with both wild- and mutant-type p53 protein, reacted in nuclei of tumour cells of 7 osteosarcomas (39%). Most of those also reacted with PAb240. PAb1801 was expressed much more frequently in other malignant bone tumours and giant-cell tumours. In addition, PAb1801 showed intranuclear positive reactions in tumour cells of a benign chondroblastoma, and reactive cells such as actively proliferating preosteoblasts in a myositis ossificans and osteoclast-like giant cells in a giant-cell tumour. The immunoelectron-microscopic observation that p53 protein was localized in euchromatic areas of nuclei of osteosarcoma cells supported the specificity of immunoreaction for p53 protein, indicating an active role of p53 protein in the regulation of DNA synthesis and transcription. These findings suggest that point mutation of the p53 gene is frequently involved in the development of osteosarcomas. PAb240 may be a useful tool not only in screening point mutations of the p53 gene in osteosarcomas but also in the differential diagnosis between osteosarcomas and reactive bone-forming lesions. Expressions of mutant p53 protein were not correlated with any clinical or pathological factors examined, although the results should be confirmed in studies of a large number of osteosarcomas.
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PMID:Analysis of mutant P53 protein in osteosarcomas and other malignant and benign lesions of bone. 841 91

A region from exon 4 to 8 of the tumour suppressor gene p53 was analysed in 60 feline tumours (30 fibrosarcomas, seven malignant histiocytomas, three lymphosarcomas, five basal cell tumours, five squamous cell carcinomas, two adenocarcinomas of tubular skin glands, one undifferentiated carcinoma of the skin, seven mammary carcinomas). Missense mutations were detected in two fibrosarcomas, one malignant fibrous histiocytoma, the undifferentiated carcinoma of the skin and one mammary carcinoma. One nonsense mutation was detected in one fibrosarcoma and one deletion/frameshift-mutation was observed in one squamous cell carcinoma.
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PMID:Presence of p53 mutations in feline neoplasms. 1068 60

Formalin-fixed, paraffin-embedded tissue from 45 soft tissue sarcomas was analysed for allelic imbalance/loss of heterozygosity (AI/LOH) of chromosome 9. The specimens consisted of 17 cases of soft tissue leiomyosarcoma (LMS), 4 cases of cutaneous LMS, 22 cases of conventional malignant fibrous histiocytoma (MFH) and 2 cases of angiomatoid fibrous histiocytoma. All cases were categorised morphologically and immunohistochemically. DNA was microdissected from normal and neoplastic tissues. AI/LOH was performed using six microsatellite markers on the 9p region. The frequency of allelic imbalance at different loci on chromosome 9p was analysed in LMS and MFH and then compared with values previously examined in synovial sarcoma and malignant peripheral nerve sheath tumour. Although AI/LOH and microsatellite instability (MSI) were more frequent in MFH, LMS and MFH groups showed similar patterns of allelic imbalance at the 9p region. Alterations of chromosome 9p have been reported in many cell lines and tumours including LMS and MFH. 9p21 region encodes p16(INK4A) and p15(INK4B). Allelic imbalance observed at 9p 21 in this study suggests that alterations of the negative cell cycle regulators may be an important step in the pathogenesis of MFH and LMS. However, the most frequent allelic imbalance was observed at 9p24 at D9S230. Alterations of this locus were very rare in synovial sarcoma and malignant peripheral nerve sheath tumours and were absent in cutaneous LMS and angiomatoid fibrous histiocytoma. This locus may point to the existence of a genetically altered tumour suppressor gene involved in the pathogenesis of LMS and MFH. Our results support the hypothesis that MFHs may represent a morphological pathway in tumour progression of LMSs.
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PMID:Leiomyosarcoma and malignant fibrous histiocytoma share similar allelic imbalance pattern at 9p. 1573 25