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)

Recent knowledge about biological role of tumor suppressor genes and their products: RB1, p53, WT1, DCC, APC/FAP, NF1, NF2, VHL, MCC and MTS1 is presented. The main approaches of these agents as physiological regulators of cell growth and proliferation are discussed. Views on the tumor suppressor genes involvement in the development of inherited and sporadic forms of cancer have been reviewed.
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PMID:[Antioncogenes--tumor suppression genes]. 933 80

Pancreatic cancer is the fifth leading cause of cancer death in the United States, and despite improvements in the results of surgical treatment for this disease, little impact has been made upon overall mortality. New advances in treatment will depend upon improved adjuvant therapy, early diagnosis, and a better understanding of tumor biology. This article summarizes the results of molecular genetic studies in pancreatic cancer and their potential clinical significance. Familial predisposition to pancreatic cancer, cytogenic studies, DNA ploidy analysis, and examination of specific oncogenes and tumor suppressor genes are reviewed. The most frequent mutations detected have been in the K-ras oncogene, which occur in 80% of pancreatic cancers. These mutations do not correlate with tumor stage or survival, but can be useful in differentiating pancreatic exocrine from endocrine tumors and chronic pancreatitis. Mutations in the p53 gene occur in approximately 50% of tumors, and appear to be an independent prognostic factor for patient survival. Mutations in the CDKN2 gene are frequently seen in sporadic pancreatic cancers, and have been implicated in cases of familial pancreatic cancer. The significance of mutations in APC, MCC, DCC, c-erbB-2, RB-1, and mismatch repair genes in the genesis of pancreatic cancer is less clear.
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PMID:The molecular genetics of pancreatic cancer. 936 57

Familial juvenile polyposis (FJP) is a hamartomatouspolyposis syndrome in which affected family members develop upper and lower gastrointestinal juvenile polyps and are at increased risk for gastrointestinal cancer. A genetic locus for FJP has not yet been identified by linkage; therefore, the objective of this study was to perform a focused genome screen in a large family segregating FJP. No evidence for linkage was found with markers near MSH2, MLH1, MCC, APC, HMPS, CDKN2A, JP1, PTEN, KRAS2, TP53, or LKB1. Linkage to FJP was established with several markers from chromosome 18q21.1. The maximum LOD score was 5.00, with marker D18S1099 (recombination fraction of .001). Analysis of critical recombinants places the FJP gene in an 11.9-cM interval bounded by D18S1118 and D18S487, a region that also contains the tumor-suppressor genes DCC and DPC4. These data demonstrate localization of a gene for FJP to chromosome 18q21.1 by linkage, and they raise the possibility that either DCC or DPC4 could be responsible for FJP.
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PMID:A gene for familial juvenile polyposis maps to chromosome 18q21.1. 954 10

Von Hippel-Lindau (VHL) disease is an inherited autosomal dominant neoplastic disorder causing central nervous system haemangioblastomas. The VHL gene (3p25-3p26) is known to be a tumour suppressor gene, with its inactivation being responsible for a predisposition to tumour development. As far as we know, the present report of VHL disease manifestation in identical twins is unique. Genetic inquiry into the family background did not reveal this disease among their progenitors. For presymptomatic diagnosis of 17 presently unaffected family members, constitutional DNA of the twins was screened for VHL germline mutations, using loss of heterozygosity studies and exon-specific DNA sequencing. To determine the influence of somatic mutations of the VHL gene in tumourigenesis, DNA of five surgically removed intracerebral haemangioblastomas of the identical twins was analyzed in comparison with their constitutional DNA by DNA sequencing of the complete VHL coding region. However, no allelic losses were found for the VHL gene or for various other tumour suppressor genes (p53, BRCA1, BRCA2, DCC, and MCC). Furthermore, no mutations were found in the constitutional DNA of either twin sister or in the DNA of all five tumour lesions. Based on our observations, we conclude that in certain VHL families, presymptomatic molecular diagnosis of the disease is not feasible and requires close clinical surveillance of all individuals at risk.
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PMID:Multiple intracerebral haemangioblastomas in identical twins with von Hippel-Lindau disease--a clinical and molecular study. 963 66

There is vast evidence in support of the idea that accumulated genetic changes (mutations) are the underlying cause of neoplasia development. This multi-step process is aptly illustrated by colorectal carcinoma (CRC), usually developing in the course of decades, and presumably requiring at least seven genetic events to complete its development. In CRC the oncogenes most frequently undergoing mutation are c-k-ras and c-myc, and among tumor suppressant genes--APC, MCC, DCC, p53. An updated model of the molecular bases for adenoma occurrence and its evolution into carcinoma is presented. Inheritance of a single gene only which has undergone mutation augments substantially the predisposition to CRC. This is noted in a clearcut manner in the hereditary syndromes familial adenomatous polyposis (FAP) and hereditary non-polypous colorectal carcinoma (HNPCC). Recent studies along these lines suggest that the genetic defect in FAP increases the incidence of tumor initiation through functional impairment of the APC gene which is a gene regulator of the enhanced colorectal mucosa proliferation. Contrarily, the defect in HNPCC involves mainly the tumor progression through mutation of the DNA repair genes (MMRs), which are regulators of the genome stability. The study of hereditary syndromes give rise to a new concept for the occurrence and development of sporadic and inherited cancer in humans.
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PMID:[The molecular biology and genetics of colorectal carcinoma]. 973 86

Objective. We studied the molecular abnormalities involved in the pathogenesis of endocrine tumors of the uterine cervix. Methods. We obtained DNA from precisely microdissected archival tissue from 15 endocrine tumors of the uterine cervix, consisting of 5 carcinoids (1 typical, 4 atypical), 2 large cell neuroendocrine carcinomas, and 8 small cell carcinomas. We investigated the presence of high-risk (types 16 and 18) and intermediate-risk (types 31 and 33) human papilloma virus (HPV) sequences, TP53 and K-ras gene mutations, and loss of heterozygosity (LOH) at 9 genes/chromosomal regions, including 3p14.2/FHIT, 3p14-p21, 3p21, 3p22-p24, 5q21-q22/APC-MCC region, 9p21/CDKN2, 11q23/MEN1, 13q/RB, and 17p/TP53. Results. HPV sequences were detected in 8 (53%) tumors, HPV 16 in 2 cases, and HPV 18 in 2 cases. LOH at 9p21 (43%) and localized 3p deletions (47%) were the most frequent allelic losses found. Allelic losses at 5q21-q22/APC-MCC region, 11q23/MEN1, and 13q/RB were infrequent. TP53 gene mutations were detected in 7 (47%) tumors (1 atypical carcinoid and 6 carcinomas). HPV sequences were demonstrated in 4 of the 7 cases with TP53 gene mutations. No K-ras mutations were detected. Conclusion. The molecular changes present in endocrine tumors of the uterine cervix have distinct features. They incorporate those present in the neuroendocrine tumors of the lung (high frequency of TP53 gene abnormalities and 9p21 deletions) with those detected in squamous cell carcinomas of the cervix (high-risk HPV sequences and localized 3p deletions).
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PMID:Molecular abnormalities associated with endocrine tumors of the uterine cervix. 988 21

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

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


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