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)

Although most gallbladder carcinomas evolve from dysplasia and carcinoma in situ, the role of gallbladder adenomas in the pathogenesis of gallbladder carcinoma is still controversial. A series of molecular changes including loss of heterozygosity (LOH) at 17p (TP53 gene), 13q (RB gene), 18q (DCC gene), and 9p21 (CDKN2a gene) chromosomal regions have been identified in dysplasias, carcinomas in situ, and invasive carcinomas of the gallbladder, whereas mutations in K- and N-ras genes are rare. To determine whether the molecular abnormalities of adenomas are similar to those found in carcinomas, we obtained extracted DNA from precisely microdissected tissue from 16 gallbladder adenomas (14 pyloric and 2 intestinal-type). We determined the presence of mutations in TP53, K- and N-ras genes, and LOH at five chromosomal regions (5q22 APC-MCC region, RB, TP53, DCC and 9p21-CDKN2a). For the TP53 mutation study, single strand conformational polymorphism (SSCP) analysis in exons 4 to 8 were performed. K- and N-ras mutations detection was performed by designed restriction fragment length polymorphism (RFLP) method and sequencing. Only a single LOH (at 5q22) was detected in a gallbladder adenoma of intestinal type. No mutations at the TP53 were detected. Four adenomas (25%) showed K-ras mutations (two in codon 12 and two in codon 61). We conclude that gallbladder adenoma lacks the molecular changes frequently detected in dysplasia, carcinoma in situ, and invasive carcinoma of the gallbladder. Likewise the occurrence of K-ras mutations at codon 12 and 61 in 25% of adenomas strongly suggests that these lesions are not precursors of invasive gallbladder carcinoma.
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PMID:Gallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas. 992 22

We succeeded in establishing a rectal cancer cell line RKK-YK from the primary lesion in a patient with rectal cancer. It took 36.2 hours for duplication. We were able to transplant the RKK-YK cell line to nude mice at a transplantation rate of 50%. The transplanted tumor exhibited histological features similar to those of the primary lesion. Cancer cells with two different degrees of differentiation, in which features of moderately differentiated adenocarcinoma and well-differentiated adenocarcinoma were observed together, were established. The levels of the tumor markers (CEA, CA19-9 and AFP) were elevated in the supernatant of the culture solution and the serum of the nude mice over time course. In the immunohistological examination of the transplanted tumor, anti-CEA, anti-CA19-9 and anti-AFP antibodies were positively stained. Molecular biological analysis revealed nor point mutation or deletion in K-ras gene exon 1 and 2, p53 gene exon 5 to 11 or MCC.
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PMID:[Establishment of alpha-fetoprotein producing human rectal cancer cell line (RKK-YK) and its features]. 1043 56

Chemotherapy and radiation therapy act predominantly through the induction of apoptosis in malignancies. Merkel cell carcinoma, an aggressive malignancy with prominent apoptosis, has proved to be sensitive to both modes to a certain degree. We used immunohistochemical methods to examine 25 Merkel cell carcinomas and 8 of their lymph node metastases to assess the status of the antiapoptotic gene bcl-2 and 2 proapoptotic genes, wild-type p53 and bax. All tumors showed prominent bax immunopositivity; 76% were positive for bcl-2, and only 28% were positive for p53, the latter presumably reflecting mutated p53. No statistically significant relationship was found between tumor immunopositivity and therapy response or survival. The widespread bax immunopositivity and the apparently low rate of p53 mutations, as suggested by the low rate of p53 immunopositivity, may be related to the presence of prominent apoptosis in Merkel cell carcinoma. The finding of bcl-2 immunopositivity in 76% of the tumors suggests that some of the tumor cells may be resistant to apoptosis-inducing agents.
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PMID:Expression of the apoptosis-related oncogenes bcl-2, bax, and p53 in Merkel cell carcinoma: can they predict treatment response and clinical outcome? 1057 19

Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of therapeutic strategies. We evaluated the antitumor activity of S-trans, trans-farnesylthiosalicylic acid (FTS), a new inhibitor of Ras signal transduction, in a newly established SCID mouse xenotransplantation model for human MCC (seven animals per group). FTS injected intraperitoneally at 5 mg/kg per day for 2 weeks up-regulated the tumor suppressor p53 and induced tumor cell apoptosis in established MCCs growing subcutaneously in SCID mice. These effects led to a statistically significant inhibition of MCC growth (P<0.002). The mean tumor weights following FTS or control treatment were 0.32+/-0.15 g and 1.08+/-0.29 g, respectively. There was no evidence of FTS related toxicity at the effective dose used. Our findings stress the notion that FTS may qualify as a novel and rational treatment approach for MCC and possibly for other tumors that rely on tyrosine kinase signaling.
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PMID:Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice. 1061 39

The p73 gene has been mapped to 1p36.33, a region which is frequently deleted in a wide variety of neoplasms including tumours of neuroectodermal origin. The p73 protein shows structural and functional homology to p53. For these reasons, p73 was considered as a positional and functional candidate tumour suppressor gene. Thus far, mutation analysis has provided no evidence for involvement of p73 in oligodendrogliomas, lung carcinoma, oesophageal carcinoma, prostatic carcinoma and hepatocellular carcinoma. In neuroblastoma, two mutations have been observed in a series of 140 tumours. In view of the occurrence of 1p deletions in Merkel cell carcinoma (MCC) and the location of p73 we decided to search for mutations in the p73 gene in five MCC cell lines and ten MCC tumours to test potential tumour suppressor function for this gene in MCC. In view of the possible complementary functions of p73 and TP53 we also examined the status of the TP53 gene. Sequence analysis of the entire coding region of the p73 gene revealed previously reported polymorphisms in four MCCs. In one MCC tumour, a mis-sense mutation located in the NH2-terminal transactivation region of the p73 gene was found. These results show that p73, analogous to neuroblastoma, is infrequently mutated in MCC. This is also the first report in which the role of TP53 in MCC has been investigated by sequencing the entire coding region of TP53. TP53 mis-sense mutations and one non-sense mutation were detected in three of 15 examined MCCs, suggesting that TP53 mutations may play a role in the pathogenesis or progression of a subset of MCCs. Moreover, typical UVB induced C to T mutations were found in one MCC cell line thus providing further evidence for sun-exposure in the aetiology of this rare skin cancer.
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PMID:Mutation analysis of P73 and TP53 in Merkel cell carcinoma. 1073 53

Twelve well-differentiated villoglandular adenocarcinomas (WDVAs) of the uterine cervix were retrospectively analyzed for the presence and specific genotype of human papillomavirus (HPV), tumor suppressor loss (p53, MCC, APC, BRCA1), cancer gene mutation (K-ras-2, exons 1 and 2, p53 exons 5 to 8), and oncogene amplification (c-erbB-2/HER-2/neu, int-2). Tissue for genetic evaluation was obtained by microdissection, using 4-micron-thick histology sections of archival, formalin-fixed, paraffin-embedded specimens. Genotyping involved nucleic acid amplification and DNA sequencing with gene-specific oligonucleotides and L1 region consensus primers for common strains of HPV. Point mutation and HPV strain determination were accomplished by DNA sequence analysis. Tumor suppressor gene loss and oncogene amplification were performed by allelic imbalance analysis in informative subjects based on DNA sequence and microsatellite-length polymorphisms. HPV was present in all tumors and consisted of type 16 (n = 5, 42%) and type 18 (n = 7, 58%) strains, which have been closely associated with cervical neoplasia. K-ras-2 and p53 genes did not manifest point mutational damage. There was no evidence of oncogene amplification or tumor suppressor gene loss. The presence of HPV in all 12 tumors supports the role of HPV infection in the molecular pathogenesis of this uncommon neoplasm. The absence of associated oncogene or tumor suppressor gene damage is consistent with indolent biological behavior and the favorable prognosis of this unusual tumor.
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PMID:Well-differentiated villoglandular adenocarcinoma of the uterine cervix: oncogene/tumor suppressor gene alterations and human papillomavirus genotyping. 1078 6

Cell growth is under the control of a variety of positive and negative signals. An imbalance of such signals results in deregulation of cell behavior. Recessive oncogenes or tumor suppressor genes, opposite to dominant oncogenes, encode important cellular proteins which could function as negative regulators of the cell cycle, i.e., cell cycle brakes. Inactivation of recessive oncogenes, by allelic deletion, loss of expression, mutation, or functional inactivation by interacting with oncogene products of DNA tumor viruses or with amplified cellular binding proteins, will lead to uncontrolled cell growth or tumor formation. Besides the classic suppressor genes such as the p53 and RB, a growing number of novel tumor suppressor genes have been identified in recent years. While some tumor suppressor genes have been found to be important for the development of a large number of human malignancies (e.g., the p53 gene), others are more tumor type-specific (e.g., the NF-1 gene). Many human cancer types showed abnormalities of multiple tumor suppressor genes, offering strong support to the concept that tumorigenesis and progression result from an accumulation of multiple genetic alterations. In this review, we will begin with an overview (gene, transcript, protein and mechanisms of action) of the tumor suppressor genes (the RB, p53, DCC, APC, MCC, WT1, VHL, MST1, and BRCA1 genes) identified to date and then discuss the specific involvement of tumor suppressor genes in human malignancies including prostate cancer. Various chromosomal regions which potentially may contain tumor suppressor genes also will be reviewed.
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PMID:Recessive oncogenes: current status. 1117 62

Twenty-three cases of basaloid squamous cell carcinoma (BSCC) and 23 stage-matched pairs of typical squamous cell carcinoma (SCC) of the oesophagus were investigated for molecular aberrations. Polymerase chain reaction (PCR) was used to detect loss of heterozygosity at the APC, RB, and MCC gene loci, while differential PCR was carried out to detect amplification of the CDK4 gene. In addition, the level of expression of the p53 and RB proteins in the tumour tissue was assessed by immunohistochemistry. Loss of heterozygosity (LOH) at the APC and MCC loci was about twice as common in BSCC as in SCC (40% vs. 21% and 33% vs. 12%, respectively), with co-existence of LOH at both loci occurring only in BSCC. LOH frequency at the RB gene locus was not remarkably different in either BSCC or SCC (20% vs. 24%, respectively). On immunohistochemistry, accumulation of p53 protein was slightly more frequent in BSCC than in SCC (61% vs. 52%), whereas the rate of loss of RB protein expression was about equal in both types of carcinoma (9% vs. 13% BSCC and SCC, respectively). There was no detectable amplification of the CDK4 gene in either type of tumour. Although the observed differences did not achieve statistical significance, this work has further highlighted possible differences between the molecular pathogenesis of BSCC and SCC.
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PMID:Comparative analysis of basaloid and typical squamous cell carcinoma of the oesophagus: a molecular biological and immunohistochemical study. 1118 Jan 60

Twenty-six gastric carcinoma and matching normal tissue DNAs, which had previously been analyzed for alterations of the APC (adenomatous polyposis coli) and MCC (mutated in colorectal cancer) genes were further investigated for the following genetic alterations: mutation and loss of heterozygosity (LOH) of the p53 gene, replication error (RER) and LOH at 12 microsatellite repeat loci, and mutation of the hMSH2 gene. In addition, 9 of the 26 gastric carcinomas were analyzed for genetic alterations using comparative genomic hybridization (CGH). Somatic mutations of the p53 gene were found to be frequent being detected in 31% of gastric carcinomas while LOH at the p53 locus was observed in 37.5% of informative cases. Loss of wild type p53 allele was detected in the majority (7 of 8) tumors found to be harboring a mutation. In the hMSH2 gene, an intronic 4 base pair insertion at 31 base pairs upstream of the beginning of exon 13 was detected in both tumor and normal tissue from one gastric carcinoma case. RER was detected in 11.5% of gastric carcinomas, at one or more microsatellite repeat loci. Of the 12 microsatellite repeat loci analyzed LOH was most frequently observed at D22S351 (30% informative cases) suggesting that a tumor suppressor gene on 22q may be important in gastric carcinogenesis. In support of this, CGH analysis carried out on 9 of the gastric carcinomas identified loss of chromosome 22 in 5 of these tumors.
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PMID:Genetic alterations in gastric cancers from British patients. 1137 3

A free-floating cell line has been established from a metastatic lesion of a Merkel cell carcinoma (MCC) patient. The cell line was characterized by immunocytochemical reactions with antibodies against the epithelial and neuroendocrine antigens: cytokeratin 20, neuron-specific enolase, chromogranin A, neurofilament protein, synaptophysin, and calcitonin. Karyotype analysis of the MCC cells showed deletion in chromosomes 3 and 7, loss of chromosome 10, and several translocations in other chromosomes. No mutation was detected in the TP53 gene, after analyzing the complete coding region. Growth factors such as basic fibroblast growth factor, transforming growth factor-beta, and nerve and epidermal growth factors had no effect on the proliferation of the cells. The differentiation-inducing agents sodium butyrate and dimethyl sulfoxide, especially the former, markedly inhibited the proliferation of the MCC cells. Aloe emodin, a natural constituent of aloe vera leaves, significantly inhibited the growth of MCC cells. Aloe emodin has been reported to be nontoxic for normal cells but to possess specific toxicity for neuroectodermal tumor cells. Differentiation-inducing agents, and aloe emodin, merit further investigation as potential agents for treating MCC.
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PMID:The effect of aloe emodin on the proliferation of a new merkel carcinoma cell line. 1180 75


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