Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53 tumour suppressor gene is intensively studied because mutations in this gene are the most common genetic alteration so far identified in human cancer. Considerable emphasis has thus been placed on characterizing the biological differences between mutant and wild-type p53 protein. This has led to the realization that in cultured cells, mutant p53 behaves like an oncogene, whereas wild-type p53 is a tumor suppressor gene. The p53 protein is also a target for the tumour virus oncogene products SV40 large T, adenovirus E1B, and human papillomavirus type 16 E6, which are all capable of forming complexes to the p53 protein. Although p53 represents an extremely important cellular regulatory molecule which is well conserved, there exists two allelic variants of wild-type human p53 that differ both in primary and confirmational structure. One variant contains an arginine at amino acid 72 (p53Arg), whereas the other form contains a proline at this residue (p53Pro). The possible implications for more than one allelic variant of wild-type human p53 in the general population is unknown. The present study was undertaken to compare some of the biological features of the different wild-type p53 variants. We present data demonstrating that there was a post-transcriptional selection against accumulation of both variants of wild-type human p53 in 3T3-A31 cells, arguing that both forms are proliferation inhibitory in these cells. Both variants of human p53 were stabilized by SV40 large T, but did not displace mouse p53 from SV40 large T. Neither allelic variant of human p53 was able to reduce significantly SV40-mediated anchorage-independent growth of 3T3-A31 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular analysis of different allelic variants of wild-type human p53. 129 28

p53 is a tumor suppressor gene that is mutated in diverse tumor types. Here we report the frequencies of common polymorphic variants at codon 72 of the p53 gene in germline DNA of lung cancer cases and controls as determined by a polymerase chain reaction strategy. The observed allelic distribution was found to be significantly different between African-Americans and Caucasians in this U.S. population. The frequency of polymorphic variants was similar in lung cancer cases and controls after adjustment for race. However, among lung cancer patients the proline variant at codon 72 was in excess in adenocarcinoma patients by comparison with other histologies.
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PMID:Allelic frequency of a p53 polymorphism in human lung cancer. 130 61

A number of glycoproteins are regulators of the complement cascade and prevent damage to cells by inappropriate activation of complement. In humans, all of them are encoded by a multigene family on chromosome I and share a characteristic structural feature, the short consensus repeats of about 61 amino acids with a constant framework of cysteine, proline, and tryptophan. We found the gene for glycoproteins of analogous structure in herpesvirus saimiri, a T-lymphotropic tumor virus of New World primates. Unspliced transcripts code for a membrane-bound 65- to 75-kDa virion surface component, while spliced mRNA instructs a secreted glycoprotein of 47 to 53 kDa. Expression of complement control proteins suggests a novel mechanism of counteracting host immune defense to prevent elimination of a virus that is capable of persisting in circulating lymphocytes.
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PMID:New member of the multigene family of complement control proteins in herpesvirus saimiri. 131 92

The 1-O-octadecyl 2-O-methyl-sn-glycerophosphocholine (ET-18-O-CH3), when incubated for 24-48h with cells in culture, exerts a highly selective cytotonic activity against a variety of tumor cells that is not seen in normal ones. In this study, we present data which indicate that this exogenous molecule altered the endogenous synthesis of the neutral ether, ester-sn-glycerols, in 2 variant cell lines of a rat colon carcinoma. ET-18-O-CH3, at 20 microM in the medium and for an incubation of 48h, inhibited the growth rates of the PRO cells which have the ability to metastasize and of the REG cells (the regressive cell line), by, respectively, 54 and 67%, as measured after [3H] thymidine uptakes. The synthesis of the ether, ester-glycerolipids was followed after an incorporation of [3H] hexadecanol into the cell lipids. The radiospecific activity of the alcohol in the ether, ester-glycerolipids was higher for the PRO cells than for the REG cells. ET-18-O-CH3 activated the incorporation of [3H] hexadecanol in the neutral ether, ester-sn-glycerols: 1.55 fold in the PRO cells, but 2.15 fold in the REG cells. No change was observed in the alkyl (alkenyl) acyl-sn-glycerophospholipids. Most of the transformed cells have a low etherase activity and are known to accumulate the ether, ester-glycerolipids, (neutral and ionic structures).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine causes a differential incorporation of hexadecanol into neutral ether ester glycerolipids of 2 variant cell lines of rat colon carcinoma. 138 72

The antineoplastic properties of suramin, a polyanionic agent with demonstrated antigrowth factor activity, are under evaluation in vitro, in vivo, and in clinical trials. Suramin has been shown to have antitumor activity in patients with advanced, hormone refractory prostate cancer. During these trials, significant resolution of osseous pain was observed in nearly three quarters of the patients treated with suramin. To evaluate the effect of suramin on bone cells, we studied the effect of suramin on bone resorption in a neonatal mouse calvarial assay. Suramin inhibited bone-resorbing activity in a dose-related fashion and had an additive effect with calcitonin. Calvaria pretreated with suramin had less bone-resorbing activity, fewer attached osteoblasts, and less medium alkaline phosphatase activity than control calvaria. Suramin also inhibited osteoclastic release of tritiated proline from labeled bone in a dose-dependent fashion. The effect of metastatic prostate carcinoma on bone is incompletely understood, but may be moderated by tumor-produced factors and/or cytokines. The effects of several such agents, therefore, were examined in combination with suramin. Bone resorption induced by PTH, epidermal growth factor, tumor necrosis factor, and a tumor-produced factor, PTH related-protein, was blocked by suramin. The ability of suramin to inhibit the bone-resorbing effects of several cytokines suggests that its mechanism may involve direct action on bone metabolism. Autoradiography performed on calvaria treated with labeled suramin demonstrated heavy deposition of suramin on the outer surface of the matrix, adjacent to osteoblasts and osteoclasts lining the outer table, suggesting that bone cells may be subject to high local concentrations of the drug, in keeping with this hypothesis.
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PMID:Suramin inhibits bone resorption and reduces osteoblast number in a neonatal mouse calvarial bone resorption assay. 142 26

Proto-oncogenes (H-ras-1 and L-myc) and tumor-suppressor gene (p53) loci have been implicated in lung carcinogenesis. DNA restriction fragment length polymorphisms at these gene loci are being evaluated in a case-control study as markers predictive of risk for cancer or of prognosis when cancer is present. The cases and controls had a cigarette-smoking history of 40 or more pack years or other abnormalities in pulmonary function tests, their ages were closely matched (64 years for cases and 61 years for controls) and the ratio of Caucasians to African Americans was close to unity (cases, 0.95:1.00, controls, 1.00:0.88). The H-ras-1 gene contains an insertion deletion polymorphism. Inheritance of rare H-ras-1 alleles, defined by MspI digestion, confers a relative risk for lung cancer of 2.0 (95% confidence interval, 0.5-7.3) for Caucasians and 3.2 (0.9-11.6) for African Americans (74 cases, 67 controls). The L-myc gene sequence has a restriction site (EcoR1) polymorphism between the second and third exons. Inheritance of restriction site-present alleles was reported to confer poor prognosis (presence of lymph node metastases) in Japanese lung cancer patients. This hypothesis was tested in both case-control study subjects (56 cases, 55 controls) and additional surgical cases (40), but no evidence was found to support the hypothesis in the U.S. population. The p53 gene is a tumor-suppressor gene that can encode either a proline or an arginine in the 72nd residue. No associations was found between the minor allele (proline) and diagnosis of lung cancer (76 cases, 68 controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of H-ras-1, L-myc, and p53 polymorphisms with lung cancer risk and prognosis. 148 64

Proline-directed protein kinase (PDPK) is characterized as a cytoplasmic oncogenic serine/threonine kinase that is activated by growth factor-mediated mechanisms and is proposed to function in mammalian somatic cells as an S phase promoting factor. The present study was undertaken to assess the hypothesis that p34cdc2/p58cyclinA PDPK is a physiologically relevant form of the p34cdc2 protein kinase that phosphorylates and inactivates the product of the retinoblastoma/osteosarcoma tumor susceptibility gene (Rb protein). In the course of these studies it was determined (fortuitously) that the p34cdc2/p58cyclinA PDPK purified from the cytosol of FM3A mouse mammary carcinoma cells was 'contaminated' by several high molecular weight substrate proteins that essentially co-purified with the protein kinase, one of which was identified as the Rb protein itself (p105Rb). High-resolution fast protein liquid chromatography (FPLC) revealed that the Rb protein co-purified with a particular subset of the PDPK heterodimer, i.e. with a single species of the 58 kDa cyclinA doublet. The subset of PDPK associated with the Rb protein exhibited somewhat lower specific enzyme activity, as judged by in vitro kinase assays and comparative Western blotting. Immunoprecipitation studies confirmed that p105Rb is physically associated with the p34cdc2/p58cyclin A PDPK. Further studies confirmed that the underphosphorylated Rb protein (p105Rb) present in G1 lysates of synchronized human MG63 osteosarcoma cells could be readily phosphorylated by purified PDPK in vitro, resulting in the characteristic shift in the apparent molecular mass (SDS-PAGE) of the Rb protein that is reported to accompany the hyperphosphorylation and functional inactivation of this protein. Moreover, the induction of the cyclin A subunit of PDPK in these synchronized MG63 cells was found to be closely correlated with the cell cycle-dependent phosphorylation of the Rb protein. From these studies it is concluded that the growth factor-sensitive PDPK is a physiological Rb kinase, which may function to inactivate the Rb protein in vivo.
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PMID:Co-purification of p34cdc2/p58cyclin A proline-directed protein kinase and the retinoblastoma tumor susceptibility gene product: interaction of an oncogenic serine/threonine protein kinase with a tumor-suppressor protein. 153 45

The p53 gene was examined in primary or metastatic tumors from six patients with rhabdomyosarcoma (RMS) and in five RMS cell lines by screening methods including single-strand conformation polymorphism analysis, the RNase protection assay, sequencing of complementary DNA subclones, and Southern blotting. Six original tumors were of embryonal histology, four alveolar, and one mixed. p53 mutations were identified in four of the six tumors or cell lines derived from tumors with embryonal histology and in one of the four with alveolar histology. Consistent with p53 allele loss, each mutation was found in the homo- or hemizygous state. One tumor showed a G to C transversion at p53 codon 213 (arginine to proline), and another showed deletion of the entire gene. The p53 mutations in cell lines included a codon 248 C to T transition (arginine to tryptophan) in RD and a codon 280 A to T transversion (arginine to serine) in RH30. The cell line CTR contained a 4-base pair deletion at codons 219/220 in exon 6 with resultant frame shift and premature termination in exon 7. These data support the role of diverse types of p53 mutations in the pathogenesis and/or progression of a significant proportion of cases of childhood RMS.
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PMID:Frequency and diversity of p53 mutations in childhood rhabdomyosarcoma. 155 27

Mutation of the p53 gene, which plays an important role in the genesis of diverse human cancers, was investigated in 23 surgical specimens of human renal cell carcinoma using the polymerase chain reaction single-strand conformation polymorphism method of analysis. Only one of the 23 tumors (4.3%) carried a mutated p53 gene, which was present in exons 7-8. Direct DNA sequencing confirmed a point mutation at codon 276 (GCC to CCC) resulting in a substitution of alanine for proline. No specific clinicopathological characteristics were observed in the case with the p53 gene mutation in human renal cell carcinoma. These observations suggest that mutation of the p53 gene is rare and thus does not contribute significantly to the genesis of this tumor.
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PMID:Infrequent mutation of p53 gene in human renal cell carcinoma detected by polymerase chain reaction single-strand conformation polymorphism analysis. 158 82

Mouse 10T1/2 cells were transfected with combinations of T24 H-ras, human c-myc and the proline 193 mutant form of p53. The three-gene ras/myc/p53 combination was significantly more efficient than single genes or double gene combinations in inducing transformed foci in vitro. An analysis of cell lines isolated after transfections with ras, ras/myc, ras/p53 and ras/myc/p53 indicated that the last combination contained significantly higher levels of ras protein than the other combinations, produced tumors in syngeneic mice with a shorter latency period, and exhibited an increased ability to form lung tumors in an in vivo experimental metastasis assay. Synergistic interactions between ras, myc and mutant p53 genes were observed in focus formation and metastasis assays, suggesting that the action of the three oncogenes in malignant transformation occurs along separate but interactive pathways. These results support a working model of oncogene cooperativity in which alterations in myc and p53 permit elevated expression of ras, which is important in a mechanism affecting both cellular transformation in vitro and tumor dissemination in vivo.
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PMID:Evidence for synergistic interactions between ras, myc and a mutant form of p53 in cellular transformation and tumor dissemination. 162 May 51


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