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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a time of rapid progress in the field of human bronchogenic carcinogenesis due to recent advances in cellular and molecular biology. Important developments over the last 10 years include establishment of methods for culturing NHBE cells under defined conditions, and molecular biological and biochemical epidemiological techniques for identifying genetic changes that are associated with malignant transformation of these cells. Most progress in defining genes associated with human carcinogenesis has been due to discoveries related to oncogenes and more recently, tumor suppressor genes. As was described in Section II.B.3.a, we now know that oncogene products serve as growth factors, growth factor receptors, and cytosolic and nuclear regulatory proteins. In addition, although the actions of putative tumor suppressor genes are less well understood, the first isolated tumor suppressor gene Rb, interacts with the products of DNA viruses which, in turn, are involved in regulation of transcription as was described in Section II.B.3.b. Thus, not surprisingly, both oncogenes and tumor suppressor genes code for classes of proteins that are known to play an important role in regulation of cell proliferation. Recently, a second gene that appears to possess tumor suppression activity (p53) has been identified on the short arm of chromosome 17 (17p). The initial data suggesting a possible tumor suppressor gene on chromosome 17p came from cytogenetic and RFLP studies associating loss of heterozygosity in the chromosome 17p13 region with tumor cells and tissues. Since the p53 gene is located in this region it was evaluated and found to be frequently or always altered in several types of tumor cells. Recently, it was determined that introduction of the wild-type p53 gene into NIH3T3 cells will inhibit subsequent malignant transformation. Thus, the preponderance of evidence now supports the hypothesis that while mutated p53 acts as an oncogene, the wild-type p53 gene codes for a tumor suppressor function. The role of balance between oncogenes and tumor suppressor genes in control of proliferation is presently an active area of investigation. As discussed, introduction of a chromosome containing a tumor suppressor gene will suppress tumorigenicity of a malignant cell line, even though that cell line possesses an active c-Ha-ras oncogene. Whether or not the level of expression of an activated oncogene is related to tumorigenicity is presently being investigated.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cellular and molecular biological aspects of human bronchogenic carcinogenesis. 219 49

We present a restriction fragment length polymorphism (RFLP) analysis of 29 benign and 30 malignant prostatic tumors, using polymorphic DNA probes to the putative tumor suppressor genes DCC (Deleted in Colorectal Carcinoma; chromosome 18q21.3), nm23-H1 (17q21.3), APC (Adenomatous Polyposis Coli; 5q21) and p53 (17p13). Six of 23 evaluable cancers (26%) showed loss of heterozygosity (LOH) at DCC; 5 were advanced stage and one was clinically localized (p < 0.05). Mapping 18q deletions, another (advanced) cancer showed LOH at a locus distal to DCC (18q22), but no LOH at DCC. Three of 15 evaluable cancers (20%), all advanced, showed LOH at APC. Three of eight (38%) cancers, of which 2 were advanced, showed LOH at p53. One high grade/stage cancer of 21 (5%) showed LOH at nm23-H1 (and also at DCC). Combining data, allelic losses at either DCC, APC, or p53 genes were seen in 13% of localized cancers, but in 71% of advanced cancers (p < 0.002). Allelic loss involving nm23-H1 is rare in prostatic carcinoma. We suggest that loss of tumor suppressor genes DCC and/or an unidentified gene located distally on chromosome 18q, APC, or p53 may influence progression in prostatic carcinoma.
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PMID:Somatic allelic loss at the DCC, APC, nm23-H1 and p53 tumor suppressor gene loci in human prostatic carcinoma. 751 Mar 45

Cancers in which mutations have been identified in putative tumor suppressor genes, such as the TP53 gene, the retinoblastoma (RBI) gene, the adenomatous polyposis coli (APC) gene, and the Wilms tumor (WTI) gene, frequently show loss of the corresponding allele on the homologous chromosome. To identify locations of tumor suppressor genes involved in uterine cancer, we examined loss of heterozygosity (LOH) by using genomic probes detecting RFLPs in 35 uterine cancers at 29 loci throughout the genome, and with highly informative microsatellite markers in 21 uterine cancers at nine putative or known tumor suppressor gene loci. High frequencies of allelic loss found at loci on 3p (71%), 9q (38%), 10q (35%), and 17p (35%) suggest that tumor suppressor genes involved in uterine carcinogenesis exist in these regions. There were no significant differences in frequencies of LOH between cancers of the uterine cervix and cancers of the uterine endometrium at any of the loci tested.
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PMID:Allelotype of uterine cancer by analysis of RFLP and microsatellite polymorphisms: frequent loss of heterozygosity on chromosome arms 3p, 9q, 10q, and 17p. 751 41

We have constructed a physical map of chromosome band 17p13, using 29 markers that had been localized to 17p13 by means of fluorescence in situ hybridization (FISH) and analysis by pulsed-field gel electrophoresis (PFGE). The map spans nearly 8 Mb of genomic DNA, and the estimated average distance between each marker is roughly 290 kb. The p13 band of chromosome 17 is thought to contain a putative tumor suppressor gene in addition and distal to TP53. Deletion mapping in a large number of breast carcinomas indicated that the tumor suppressor gene lies between the loci defined by cC117-708 (D17S878) and p144D6 (D17S34), which are an estimated 7 Mb apart. Our results should contribute to construction of a contig map of chromosome band 17p13 with cosmid and/or YAC (yeast artificial chromosome) clones, and to isolation of the putative tumor suppressor gene.
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PMID:Detailed analysis of loss of heterozygosity on chromosome band 17p13 in breast carcinoma on the basis of a high-resolution physical map with 29 markers. 751 59

The specific transfer of normal chromosomes via microcell fusion has been instrumental in identifying putative tumor suppressor gene loci in a variety of human cancers. Using this same technique it has been proposed that the tumorigenicity of the human fibrosarcoma cell line HT1080 is controlled by functionally distinct tumor suppressor genes on human chromosomes I and II. To address these results and perhaps further localize the suppressive effect to particular regions on these two chromosomes, we transferred into HT1080 seven different fibroblast-derived human chromosomes containing either intact or discrete portions of chromosome I or II. Interestingly, we found no evidence of genes on these chromosomes that could alter the growth of HT1080 either in vitro or in vivo. Based on these results we were left with the possibility that a gene, or genes, residing on an entirely different chromosome(s) was involved in the tumorigenesis of HT1080. Since TP53 mutation has been documented in a variety of human tumor types, and we found both copies of TP53 to be mutated in HT1080, we were prompted to examine its role by both cDNA transfection and chromosome transfer. Although by cDNA transfection we found that expression of exogenous wild-type TP53 was incompatible with continued proliferation of HT1080 cells in vitro, chromosome 17 transfer studies revealed that a more physiologic expression of exogenous wild-type TP53 could be tolerated in vitro while being completely incompatible with growth in vivo. These studies demonstrate a differential effect of TP53 growth inhibition and clearly show that TP53 tumor suppressing function can be independent from its potent growth suppressing effect in vitro.
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PMID:Evidence that wild-type TP53, and not genes on either chromosome 1 or 11, controls the tumorigenic phenotype of the human fibrosarcoma HT1080. 751 49

To investigate genetic features of esophageal cancer, we have examined 93 squamous cell carcinomas of the esophagus for loss of heterozygosity (LOH), using 41 restriction fragment length polymorphism (RFLP) markers representing all autosomal chromosomes. Allelic losses at frequencies of at least 30% were observed at loci on chromosomal arms 3p (35%), 3q (30%), 5q (36%), 9p (57%), 9q (60%), 10p (33%), 13q (43%), 17p (62%), 17q (46%), 18q (38%), 19q (32%), and 21q (37%). These results suggest that several putative tumor suppressor genes, in addition to the cyclin D and TP53 genes that are sometimes mutated in esophageal carcinomas, may be associated with development and/or progression of esophageal cancer. By a comparison of LOH on each chromosomal arm with clinicopathological parameters, we have found a significant correlation between LOH on 19q and regional lymph node metastases. Interestingly, the frequency of LOH on 17q was significantly higher in tumors in female patients (12 of 14 cases) than in those in male patients (20 of 56 cases) (P = 0.0009 by Fisher's exact test). Furthermore, we examined for mutations of the APC gene on chromosome arm 5q. Screening of nearly one third of the APC coding region, including the MCR (mutation cluster region), revealed no alterations. Therefore, although allelic loss at the APC locus is frequent in squamous cell carcinomas of the esophagus, it is likely that a gene on 5q other than APC is involved in esophageal tumorigenesis.
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PMID:Allelotype study of esophageal carcinoma. 752 40

Non-melanoma skin cancer is common and offers unrivaled opportunities to relate genetic changes to clinical and biologic behavior. Recent technical advances in molecular biology render genetic analysis of even the smallest skin cancers possible. In this review I will discuss the role of p53 gene in skin carcinogenesis, the relation between p53 immunostaining and p53 mutation, and recent evidence for the involvement of putative tumor suppressor genes both on chromosome 9 and other chromosomes in non-melanoma skin cancer.
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PMID:Genetic alterations in non-melanoma skin cancer. 779 10

Using polymerase chain reaction amplification of microsatellite regions in DNA from 11 epithelial dysplasias of the esophagus and 21 early squamous cell carcinomas, we were able to detect frequent loss of heterozygosity (LOH) on chromosomes 3p21.3 and 9q31 even in low-grade dysplasias. In contrast, we observed frequent LOHs on chromosomes 9p22 and 17p13 (TP53 locus) only in high-grade dysplasias and carcinomas, but not in any low-grade dysplasias. Analysis of LOH at the same four chromosomal regions in DNA of five additional minimal carcinomas and accompanying dysplastic lesions revealed loss of alleles at the loci on 3p21.3 and 9q31 throughout various degrees of dysplasia and carcinoma; again, LOHs on 9p22 and 17p13 occurred only in high-grade dysplasia and carcinoma in situ. Our results indicated that inactivation of putative tumor suppressor genes on 3p21.3 and 9q31 may be early genetic events during esophageal carcinogenesis, and that additional genetic alterations on 9p22 and 17p13 probably play roles in progression.
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PMID:Accumulation of genetic alterations during esophageal carcinogenesis. 787 13

The oncogenic transformation of epidermal melanocytes produces primary cutaneous melanoma. In this article, previously published cytogenetic, biochemical, molecular biology, and cell biology studies of cutaneous melanoma oncogenesis are reviewed. A variety of laboratory animal models have been developed for studies of the induction of melanoma, including mice, the laboratory opossum Monodelphis domestica, Sinclair swine, and Xiphophorus fish. Some of the advantages and disadvantages of these animal models are presented for comparison to human melanoma. Cytogenetic and loss of heterozygosity studies over the past decade have demonstrated that human metastatic melanomas contain numerous chromosomal abnormalities, and that normal melanocytes have putative tumor suppressor genes that are presumably deleted or inactivated in transformed melanocytes to yield malignant melanoma cells. The status of research efforts to identify the putative tumor suppressor genes of human chromosomes 1p, 6q, and 9p, implicated in sporadic and familial melanoma, is presented. Furthermore, the roles of ultraviolet radiation, genetic susceptibility, dominant oncogenes, growth factors, the p53 gene, antioxidant enzymes, and DNA tumor viruses in the formation of cutaneous primary melanoma are discussed.
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PMID:Recent advances in cutaneous melanoma oncogenesis research. 791 46

To determine the role of the p53 gene in the pathogenesis of basal cell carcinoma (BCC), we screened mutations of the gene in 11 cases of BCCs using the polymerase chain reaction (PCR) and single-stranded conformation polymorphism (SSCP). However, in all the coding exons of the gene analysed, no evidence suggesting the mutations were obtained. On the other hand, in 2 of 5 informative cases of our BCCs (40%) we found loss of heterozygosity (LOH) for loci on chromosome 9q31 which is linked to the Gorlin syndrome, that predisposes to BCC. Therefore, we suggest that a putative tumor suppressor gene on the region of 9q, but not p53 gene, plays a critical role in the pathogenesis of BCC, independent of race.
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PMID:Analysis of p53 gene mutations and loss of heterozygosity for loci on chromosome 9q in basal cell carcinoma. 818 55


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