Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with bilateral retinoblastoma and subsequent multiple primary osteosarcomas has been described previously. Osteosarcoma cell lines established from this patient were shown to express a shortened RB1 mRNA transcript and no detectable normal Rb protein. We now show that the osteosarcoma cell lines have lost one TP53 allele and contain a mutation in exon 8 codon 286 [GAA to AAA (Glu to Lys)] in the remaining allele. Consequently, the osteosarcoma cell lines have no normal Rb protein and no normal p53 protein. Neither constitutional DNA nor DNA extracted from a retinoblastoma of the left eye of the patient contained the TP53 mutation, suggesting that the TP53 mutation in the osteosarcoma cells may represent a tumor-promoting mutation, which confers a selective growth advantage. If both RB1 and TP53 are involved in the initiation of osteosarcoma, the mechanisms for development of the retinoblastoma and osteosarcoma tumors are different.
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PMID:A TP53 mutation detected in cells established from an osteosarcoma, but not in the retinoblastoma of a patient with bilateral retinoblastoma and multiple primary osteosarcomas. 133 9

Osteosarcoma tumorigenesis is consistent with a model by which tumorigenesis results if both alleles at the retinoblastoma susceptibility locus (RBI) are altered. Additional genetic evidence strongly suggests that another obligate event in osteosarcoma tumorigenesis is the homozygous alteration of another gene, p53. Both the RB1 gene and p53 have been proposed to act as tumor-suppressor genes, suggesting that, in this instance, tumorigenesis is the result of the loss of gene function of these two genes, rather than a gain of function.
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PMID:Molecular genetic considerations in osteosarcoma. 167 82

Osteosarcoma is the most common malignant bone tumor in children and adolescents. The tumor, which is composed of malignant spindle cells that produce osteoid, typically occurs in the diaphyseal region of long bones; about half of all osteosarcomas arise in the distal femur or proximal tibia. Clinically detectable metastases are present in about 20% of patients at diagnosis, and most patients have subclinical metastases. Effective therapy with complete surgical resection of tumor and intensive multiagent chemotherapy results in the cure of over 50% of patients with osteosarcoma. Recent developments of importance include an improved understanding of the importance of the p53 gene in the pathogenesis of osteosarcoma, the description of preclinical models, the development of improved imaging techniques for determining tumor extent and responsiveness to chemotherapy, and refinements in therapy.
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PMID:Recent developments in genetic mechanisms, assessment, and treatment of osteosarcomas. 193 29

Osteosarcoma is the most frequent childhood bone cancer (Tebbi, C. K., and Gaeta, J. Pediatr. Ann., 17:285-300, 1988). Using Southern blot mapping, we found that 11 of 60 (18%) osteosarcomas had altered restriction patterns of the p53 gene and that six of these had loss of the other p53 allele. In contrast, no alteration of the p53 gene was detected in 50 samples from other types of sarcomas. Fifty % of osteosarcoma cell lines (4 of 8) also had gross rearrangements of one p53 allele with loss of the second allele, and these had no detectable p53 mRNA. Osteosarcoma cell lines with no detectable alteration of the p53 gene contained abundant p53 transcripts. Taken together, data show that human osteosarcomas can have rearrangements of the p53 gene; these rearrangements may cause loss of normal constraints on cellular growth.
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PMID:Frequency and structure of p53 rearrangements in human osteosarcoma. 225 37

Alterations in the p53 tumor suppressor gene have been implicated in the genesis and/or progression of the majority of human cancers, including osteosarcoma. Stabilization of the protein by mutation or interaction with other proteins prolongs its half-life, rendering it detectable by immunohistochemistry. Osteosarcoma is the most common primary canine bone tumor and is characterized by frequent early metastases. Multilobular tumors of bone involve primarily flat bones of the head and are low-grade malignancies with lower metastatic potential. The objectives of this study were to determine the prevalence of p53 protein overexpression in 106 osteogenic tumors of dogs using an indirect immunohistochemical method and to compare p53 overexpression between tumors with different clinical behavior. A polyclonal p53 antibody (CM-1) served as the primary antibody. Tumors were scored based upon an estimate of the percentage of tumor cells stained. Significant differences in the prevalence of overexpression were observed between osteosarcomas (72%) and multilobular tumors of bone (20%, P = 0.0020). Osteosarcomas of the appendicular skeleton had a significantly higher prevalence of p53 overexpression (84%) than did osteosarcomas of the axial skeleton (56%, P = 0.0060). Our results show that p53 tumor suppressor protein is overexpressed in the majority of canine osteosarcomas. The higher prevalence of overexpression in osteosarcomas versus multilobular tumors of bone and in osteosarcomas of the appendicular skeleton versus those of the axial skeleton suggests that alterations in p53 expression correlate with highly aggressive tumor behavior.
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PMID:p53 tumor suppressor protein overexpression in osteogenic tumors of dogs. 880 15

The key role of p53 and Rb alterations in human osteosarcoma is clear. For example, osteosarcoma is common in individuals inheriting mutant p53 or Rb genes. Osteosarcoma in dogs is similar to humans by histology, site, gender ratio and several other biological parameters. To study whether this similarity extends to the molecular level, 21 canine osteosarcomas were analyzed for alterations of p53, Rb and MDM2. MDM2 is a normal cell protein which antagonizes p53, amplification is seen in some human sarcomas. The gross structure of the p53, Rb and MDM2 genes was examined by Southern blotting. No deletions or rearrangements of the p53 or Rb genes were detected. The absence of gross gene alterations affecting these tumor suppressor genes is a significant difference between the disease in dogs and humans, since rearrangements or deletions of the p53 or Rb genes occur in 20-30 per cent of human osteosarcomas. The MDM2 gene appeared to be duplicated in one canine tumor but no cases of significant amplification were detected. Expression of normal Rb was detected in all cases. Mutations of the p53 gene were found in 38 percent of canine osteosarcomas. Analysis of mutations revealed a predominance of spontaneous mutation. These finding emphasize the key role that alterations of p53 have in the development of osteosarcoma in dogs and humans.
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PMID:Status of the p53, Rb and MDM2 genes in canine osteosarcoma. 989 8

Osteosarcoma is one of the most commonly biopsied primary tumor of bone. High-grade osteosarcomas in particular exhibit a wide spectrum of cytogenetic changes. Molecular cytogenetic studies on osteosarcomas have shown that genomic amplification, especially of both the TP53-binding MDM2 gene and the flanking SAS gene, plays an important role in the biology of these tumors. We applied CGH in order to obtain a global view of DNA-sequence losses and gains in osteosarcoma. CGH was performed on 20 high-grade medullary osteosarcomas (13 primary tumors prior to chemotherapy, 5 tumors after chemotherapy, 2 established cell lines [MB63, HOS58]) using genomic DNA of snap-frozen tumor specimens. CGH revealed DNA copy number aberrations, mostly gains, in all the tumors studied with an average of 18.5 aberrations/tumor (range 8-32). High-level amplifications were observed in all cases (average 4.1 amplifications/tumor [range 1-10]). Amplicons affecting at least five tumors were mapped to 1p21-31 (9/20 cases), 3q25-qter (6/20), 6p12-21 (6/20), 8q12-qter (10/20), 12p11-12 (9/20), 12q12-15 (enclosing MDM2 and SAS loci, 7/20). Losses were most frequently seen at 3p, 10q, 11p and 13 (all 10/20). In conclusion, our CGH data indicated that genomic amplification plays an important role in the biology of osteosarcoma. CGH demonstrated the complexity of genetic aberrations in osteosarcomas. The detection of novel non-random DNA amplifications in our study has defined regions for further targeted molecular genetic research aimed at identifying those oncogenes that are characteristic of osteosarcoma development.
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PMID:[Comparative genomic hybridization (CGH) for detecting a heretofore undescribed amplified chromosomal segment in high-grade medullary osteosarcoma]. 1009 31

Osteosarcoma is an uncommon tumor. Family occurrence of osteosarcoma is even rarer. Four cases of osteosarcoma in two siblings and in a father and son treated at our Institute with surgery and chemotherapy are reported. These patients had no other tumors in their family history, and had negative p53 mutations in exons 5-9 by SSCP analysis. RB, CDK4, MDM2, c-myc, c-fos, and p53 gene expression, which are the major genes involved in osteosarcoma susceptibility, were studied. Our results revealed an inactive form of p53 sporadically seen in the samples, a total loss of Rb protein expression, an increased expression of Cdk4, MDM2, c-fos, and c-myc proteins which literature currently reports being the principal alterations found in osteosarcoma. These findings confirm that specific genetic alterations occur in osteosarcoma pathogenesis.
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PMID:Osteosarcoma in blood relatives. 1111 84

Osteosarcoma is the most frequent highly malignant bone-tumor with a peak manifestation during the second and third decade of life. Although survival rate increased up to 60-70% within the last 20 years, the problem of non-response to chemotherapy remains. Initial tumor size and response to neoadjuvant chemotherapy are the most accepted prognostic factors used for postoperative stratification of chemotherapy. The identification of patients with a bad response to therapy at the time of diagnosis would facilitate already a preoperative stratification of chemotherapy or a more aggressive regime to increase survival. This review reflects on recently described molecular markers but not on clinical parameters in human osteosarcoma with respect to their prognostic potential. This includes p53, the p-glycoprotein, the multidrug resistance gene, the humen epidermal growth factor receptor and metallothionein expression. Heat shock proteins have recently become important in osteosarcoma because of their prognostic value and their role in drug resistance. A short overview of serological markers is also given. Further results on drug resistance and survival may be provided by ongoing studies, which investigate the role of proteins of the apoptotic and antiapoptotic families in human osteosarcoma.
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PMID:Proteins expressed in osteosarcoma and serum levels as prognostic factors. 1116 28

Osteosarcoma is a malignant tumor with heterogeneous features both in histological and biological aspects. We have established three tumorigenic cell lines, MMOS1, MMOS2, and MMOS3, from three independent tumors that developed in nude mice after the inoculation of MMC2, an osteoblast-like cell line derived from p53-/- mice. Expression patterns of the osteoblast-related genes showed a marked difference between MMOS2 and the other two cell lines, and were correlated well with the features of the original tumors, ranging from an osteoblastic osteosarcoma (MMOS2) to tumors with scarce or no osteoid formation (MMOS1 and MMOS3). The properties of malignant cells also varied in the three cell lines. MMOS1, which was the most serum-dependent in vitro, developed markedly larger tumors in vivo than the other two cell lines. MMOS3 showed the fastest growth in low-serum conditions and produced the largest number of colonies in soft agar, but did not develop lung metastases, whereas MMOS1 and MMOS2 developed lung metastases with a frequency of 30 and 50%. These data suggest that the biological activities in vivo do not necessarily reflect those in vitro. Because the three tumorigenic cell lines share MMC2 as a common precursor, our data showed an example that the heterogeneity of osteosarcoma was created by genetic alterations that took place during the transformation process of each tumor.
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PMID:Morphological and biological heterogeneity of three tumorigenic cell lines derived from a single p53-/- osteoblast-like cell line, MMC2. 1204 66


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