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)

The ability to efficiently detect DNA polymorphisms is essential for the completion of a high-resolution polymorphic linkage map of the human genome. Currently the most informative polymorphisms are the multiallelic dinucleotide repeat polymorphisms. However, many gene sequences lack an associated dinucleotide repeat sequence. We used GC-clamped denaturing gradient gel electrophoresis to screen for DNA polymorphisms in the following six gene sequences: MCC, p53, prealbumin (transthyretin), rhodopsin, S-antigen, and TGF-alpha. A single-base sequence polymorphism was identified in each of these gene sequences. Some of these polymorphisms were multiallelic and highly informative. Our results demonstrate the value of denaturing gradient gel electrophoresis for both identifying and analyzing human DNA polymorphisms. The ability to detect highly informative polymorphisms within gene sequences will greatly contribute to a gene-based polymorphic linkage map.
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PMID:Detection of multiallele polymorphisms within gene sequences by GC-clamped denaturing gradient gel electrophoresis. 153 94

In vitro and in vivo metastatic variants derived from Lewis lung carcinoma (3LL) were examined for the level of the expression of several growth-regulated genes, oncogenes, and transforming growth factor (TGF) genes. To determine whether the proliferative advantage of metastatic cells is due to an increased growth fraction of the cell population or to a deregulated expression of some growth-regulated genes, the mRNA levels of the S-phase-specific H3 histone gene were compared with that of some cell cycle-related genes (vimentin, calcyclin, c-myc, and p53) and oncogenes (Ki-ras, Ha-ras, c-sis, c-src, c-fes, and c-erb). In addition, to evaluate whether an autocrine pattern of cell proliferation is responsible for the proliferative advantage of metastatic cells, the level of the expression of TGF genes (alpha and beta 1) was studied. Northern blot analysis demonstrated that in 3LL metastatic variants the expression of TGF-alpha as well as the expression of all growth-regulated genes and oncogenes studied are similar. Only the TGF-beta 1 gene is expressed at higher levels in highly metastatic 3LL variants maintained either in vitro or in vivo. Data suggest that the proliferative advantage of 3LL metastatic cells is not due to a deregulated expression of some growth-regulated genes and oncogenes, but more likely is acquired through the expression of genes which might interfere with the ability of the tumor cells to escape hostile microenvironmental conditions.
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PMID:Differential expression of transforming growth factor-beta 1 gene in 3LL metastatic variants. 191 69

Amplification of the c-myc gene has been frequently reported in breast carcinomas. However the precise function of the c-myc protein is still unknown and the nature of the selective advantage offered to a cell by an overexpression of such a protein is unclear. We are addressing this question using the SW 613-S human breast carcinoma cell line as a model system. This cell line harbours an amplified c-myc gene and a mutated c-Ki-ras gene. By various criteria the amplified c-myc gene of SW613-S cells appears undistinguishable from a normal human c-myc gene. The SW613-S cell line is heterogeneous: it contains cells with a high level of amplification and carrying the extra copies of the c-myc gene in double minute chromosomes (DMs) and cells with few c-myc genes integrated into chromosomes. DM-containing cells are progressively lost upon in vitro cultivation but are selected for during in vivo growth, as tumors in nude mice, or by cultivating the cells in a chemically defined, serum-free medium or under conditions preventing anchorage. Clones with different levels of amplification and different chromosomal localization of the c-myc copies were isolated from the SW 613-S cell population. Those with a high level of amplification and expression of the c-myc gene are tumorigenic in nude mice, whereas those with a low level are not. Introduction of c-myc gene copies by transfection confers tumorigenicity to the nontumorigenic clones, indicating that a high level of amplification of the c-myc gene contributes to the tumorigenic phenotype of SW 613-S cells. Tumorigenic clones grow unattached, are able to proliferate in a chemically defined medium, and produce high levels of several growth factors (e.g. TGF-alpha, IGF2). Nontumorigenic clones are more dependent upon anchorage for growth, show a restricted growth in defined medium, and produce low or undetectable level of the growth factors tested. We have identified several genes, besides c-myc, the expression level of which is markedly different in the two types of clones. TGF-alpha, IGF2, PDGF-A, int-2, cytokeratins K8 and K18 and ferritin H chain are overexpressed in tumorigenic clones. In contrast, c-erbB1 (EGF receptor), c-jun, vimentin and p53 are expressed at a higher level in the nontumorigenic clones. Finally the major histocompatibility class I antigens, ferritin L chain, TGF-beta and c-Ki-ras, are examples of genes expressed at the same level in both types of clones.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The human breast carcinoma cell line SW 613-S: an experimental system to study tumor heterogeneity in relation to c-myc amplification, growth factor production and other markers (review). 268 29

Six colon cancer cell lines, 13 colon tumors and ten normal colon tissues were analyzed for RNA expression using probes for c-myc, c-k-ras, c-myb, and c-fos and for the p53, TGF-alpha, and EGF receptor genes. No aberrant transcripts were detected. Levels of expression in tumors ranged from two-fold below that of normal tissue when the v-fos probe was used to 10 fold above the normal level when the c-myc probe was used. Enhanced c-myc expression was also observed in the cell lines. Southern and DNA dot blot analyses revealed c-myc amplification in three of the six cell lines.
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PMID:Oncogene expression in adenocarcinomas of the colon and in colon tumor-derived cell lines. 328 75

Physical and chemical agents can damage the genome. Part of the protective response to this damage is the increased expression of p53. p53, a transcription factor, controls the expression of genes, leading to cell cycle arrest and apoptosis. Another protective mechanism is the proliferative response required to replace the damaged cells. This proliferation is likely to be signaled by growth factors. In this communication, we show that the transforming growth factor alpha (TGF-alpha) gene is a direct target for p53-mediated transcriptional activation. In a stable cell line containing an inducible p53 construct, p53 induction leads to a threefold accumulation of the native TGF-alpha mRNA. IN cotransfection assays using a TGF-alpha promoter reporter construct, we show that expression of wild-type but not mutant p53 increases transcriptional activity of the TGF-alpha promoter by approximately 2.5-fold. In vitro, wild-type p53 binds to a consensus binding site found in the proximal portion of the promoter, and this sequence is necessary for the p53 transcriptional response. Furthermore, this element confers p53 induction to the otherwise nonresponsive adenovirus major late promoter. In addition to these results, we found that the TGF-alpha promoter contains a nonconsensus but functional TATA box-binding protein-binding site approximately 30 bp upstream of the transcription start site. Although p53 can repress transcription from promoters containing a TATA box, the nonconsensus TGF-alpha TATA motif is resistant to this effect. On the basis of these results, we propose that p53 may play a dual role, which includes both the elimination of irreparably genetically damage cells and the proliferative response necessary for their replacement, in the response to physical-chemical damage.
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PMID:p53 stimulates transcription from the human transforming growth factor alpha promoter: a potential growth-stimulatory role for p53. 765 86

Growth of thyroid cancer cells is stimulated by various growth factors via signal transduction pathways. TSH, EGF, IGF, and TGF-alpha stimulate and TGF-beta inhibits thyroid cell growth. TSH stimulates thyroid cells via both the adenylate cyclase-PKA and the PLC-PKC-Ca signal transduction pathways. TSH-r, ras, gsp, ret, trk, and myc are oncogenes that are activated in some thyroid neoplasms. P53 and RB are tumor suppressor genes that are inactivated in some thyroid cancers.
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PMID:Thyroid growth factors, signal transduction pathways, and oncogenes. 774 50

Over-expression of transforming growth factor-alpha (TGF-alpha) is consistently seen in spontaneous transformants of rat liver derived epithelial cells (RLE phi 13) and has been implicated in the transformation of other cultured cells. We have constitutively over-expressed TGF-alpha in RLE phi 13 cells, which are known to express epidermal growth factor receptors, to determine if TGF-alpha over-expression plays a role in transformation or differentiation, or both, of these cells. Early passage RLE phi 13 cells were infected with a replication-defective murine retrovirus that expresses both the full length coding sequence for human TGF-alpha and the neomycin-resistance gene. Integration of the transcriptionally active provirus and expression of TGF-alpha mRNA were confirmed. Neither morphologic transformation nor molecular evidence for differentiation was noted in TGF-alpha-producing clones. However, these clones did exhibit an accelerated growth rate, increased expression of several cell cycle related genes including mitotic cyclic B1, proliferating cell nuclear antigen, c-myc, and p53 as well as increased expression of the preneoplastic marker enzyme, glutathione-S-transferase. This suggests that over-expression of TGF-alpha results in increased cell cycling, and that subsequent events must be necessary for cellular transformation or differentiation or both.
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PMID:Constitutive over-expression of transforming growth factor-alpha in rat liver epithelial cells leads to increased cell cycling without transformation. 782 Mar 13

An immunohistochemical study of 155 squamous cell carcinomas of the oesophagus, squamous epithelium adjacent to the tumour (n = 80), dysplastic epithelium (n = 16) and controls (n = 23) indicates that Ki67 and p53 expression is frequently present in premalignant oesophageal lesions and their related squamous cell carcinomas. Positive expression of both antibodies in apparently normal epithelium can signify early steps of malignant transformation of oesophageal epithelium and can serve in the detection of early precancerous lesions. The expression of growth factors EGF and TGF-alpha was higher in carcinomas and dysplastic lesions than in apparently normal squamous epithelium. EGF expression was unevenly distributed according to histological grade, indicating a lack of EGF immunoreactivity in poorly differentiated oesophageal carcinomas.
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PMID:p53 gene mutants expression, cellular proliferation and differentiation in oesophageal carcinoma and non-cancerous epithelium. 816 40

Human fetal liver cells were cultured in serum free media enriched with hydrocortisone and infected with retrovirus containing SV40 large T gene. Replicating colonies with G-418 resistance developed in 50 days through 23 passages, while none grew in control dishes. After a crisis of 3 months duration, three colonies resumed active proliferation for over 15 months through 60 passages and became immortalized. These cells had epithelioid morphology, and were stained positively for CK-18. Southern blot and immunocytochemistry demonstrated the presence and expression of SV40 T-antigen in the immortalized cell lines. The cells expressed human albumin, especially in those while in cycle. Accumulation of p53 protein in the cell nuclei and strong expression of TGF-alpha as shown by immunocytochemistry explained at least partly the mechanism of unlimited growth of these immortalized human hepatocytes. These cells did not show anchorage-dependent growth in soft agar, nor did tumor form when inoculated into nude mice. These immortalized, differentiated, non-malignant human fetal hepatocyte lines may be useful for further studies.
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PMID:[Establishment and mechanistic characterization of SV40 T antigen immortalized human fetal hepatocytes]. 820 Feb 77

The purpose of this study was to investigate and to compare, by in situ hybridization, gene expression of IL-1 beta, IL-8, TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-alpha, p53 and c-myc in lesions and in non-involved skin of patients with psoriasis. All lesional skin biopsies showed overexpression of IL-1 beta, IL-8 TGF-alpha mRNAs. IL-1 beta hybridization signals were strong in a small number of cells localized predominantly in the dermal papillae and in the suprapapillary epidermis. Overexpression of TGF-alpha was observed in all suprabasal keratinocytes, whereas strongly elevated IL-8 mRNA expression was found to be restricted to clusters of suprabasal keratinocytes. TGF-beta 3, p53 and c-myc transcripts were clearly detected in the epidermis of all biopsies, although expression levels were comparable in lesional and non-lesional skin.
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PMID:In situ hybridization analysis of cytokine, proto-oncogene and tumour suppressor gene expression in psoriasis. 821 83


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