Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have established two cell lines of hepatocellular carcinoma [Hep-KANO, clone 1 (CL-1) and clone 2 (CL-2)] from tissue obtained at autopsy of a hepatitis B virus (HBV) carrier without histological signs of hepatitis or liver cirrhosis. These cell lines differed considerably from each other in morphology, proliferation pattern, alpha-fetoprotein secretion, albumin synthesis, cytokine secretion, modal chromosome number and transplantability to nude mice. Histologic examinations also revealed differences between them. Amplification of N-myc, L-myc, H-ras, K-ras, N-ras, c-erb-B and c-erb-B-2 and rearrangement of p53 were not found in either of the cell lines. However, CL-1 and CL-2 showed an identical HBV-DNA integration pattern. A 4-fold amplification of c-myc was observed in CL-1, but not in CL-2. Hep-KANO cell lines, CL-1 and CL-2 may be useful in clarifying the question of whether hepatocarcinogenesis is directly caused by HBV infection.
 ...
PMID:Characteristics of human hepatocellular carcinoma cell lines (Hep-KANO) derived from a non-hepatitic, non-cirrhotic hepatitis B virus carrier. 782 95

The L-myc and p53 genes have been implicated in lung cancer. Both of these genes have restriction fragment length polymorphisms (RFLPs) that could account for differential expression or activity of variant forms. An EcoRI restriction site in the L-myc gene was previously reported to be a predictor of poor prognosis in Japanese lung cancer patients. There are several RFLPs in the p53 gene. In exon 4 there is a polymorphism that codes for either an arginine or proline residue at codon 72. We previously reported the frequency of DNA-RFLPs at these gene loci revealed by EcoRI and AccII respectively. Here we report results from a study comparing lung cancer cases (n = 31) with chronic obstructive pulmonary disease controls (n = 49). No association was found between these RFLPs and disease status. Previous observations that the frequencies of these RFLPs varied by race were confirmed. The p53 arginine allele was found to be more common in Caucasians (0.71) than African-Americans (0.50). The EcoRI restriction site present allele in L-myc was more frequent in African-Americans (0.71) than Caucasians (0.49). Thus, the allelic frequency for L-myc was similar in African-Americans to that reported for Japanese, and the allelic frequency for p53 was similar in Caucasians to that reported for Japanese.
 ...
PMID:Determination of the allelic frequencies of an L-myc and a p53 polymorphism in human lung cancer. 790 8

We have performed a comprehensive analysis of the DNA copy number changes that occur in 18 small cell lung carcinoma cell lines using comparative genomic hybridization (Kallioniemi et al., Science (Washington DC). 258: 818-821, 1992). DNA copy number abnormalities detected in this study include previously identified increases at 1p22-32 (L-myc), 2p24-25 (N-myc), and 8q24 (c-myc) and decreases at 17p13 (p53), 13q14 (RB), and 3p. In addition, novel DNA copy number increases were detected at 5p, 1q24, and Xq26, and novel decreases were found at 22q12.1-13.1, 10q26, and 16p11.2. Many of the most common DNA copy number changes revealed are at loci not previously recognized to be important in small cell lung cancer. In addition, a number of the DNA copy number changes, including increases at 1p22-32, 2p24-25, and 3q22-25 and a decrease on 18p, were found to occur preferentially in small cell lung carcinoma lines of the "variant" phenotype. This correlation suggests that genes may reside at these loci whose overexpression or inactivation contributes to the radiation resistance or aggressive growth phenotypes characteristic of this subtype of small cell lung carcinoma.
 ...
PMID:Identification of frequent novel genetic alterations in small cell lung carcinoma. 792 22

In all normal cells, two type of genes, oncogenes and anti-oncogenes, are expressed and control cell proliferation and differentiation. Cell growth is stimulated by oncogenes and inhibited by anti-oncogenes. Cancerization involves loss of control due to defective gene expression either by overexpression of a normal protein (loss of quantitative control) or expression of an abnormal protein (loss of qualitative control). Several oncogenes have been identified. They include three oncogenes, c-myc, N-myc and L-myc, known to be overexpressed in small-cell carcinomas of the lung. Point mutations of the oncogene K-ras is found in 15 to 30% of adenoma carcinomas, especially in smokers. Loss of anti-oncogene function has also been described in processes leading to lung cancer. Chromosome abnormalities, for example the 3p14-23 deletion described in 1982, are found in 100% of small-cell carcinomas and in 50% of non-small-cell carcinomas. This deletion is never found in normal tissue. The gene involved has not yet been cloned. Other mutations or deletions include the RB gene, necessary for neuroendocrine differentiation, and the p53 gene which has undergone mutation in 50% of the non-small-cell carcinomas and 70% of the small-cell carcinomas. These acquired mutations are strongly associated with tobacco smoking. Oncogenes and anti-oncogenes play an important role in the complex step-wise process leading to cancerization. As tumour characterization becomes more precise and precancerous states better controlled, future treatments may relief on inhibiting tumoural growth by using drugs which would substitute for the lost effect of anti-oncogenes or inhibit activation of an oncogene. But at the present time, it is still difficult to define criteria predicting high risk of postoperative relapse or resistance and further studies investigating the correlation between genetic abnormalities and clinical staging and survival curves are required.
 ...
PMID:[Oncogenes and anti-oncogenes in lung cancer]. 820 81

A new cell line, CUMC-6, has been derived from an invasive nonkeratinizing squamous cell carcinoma of the uterine cervix in a 31-year-old patient. It has been maintained in long-term culture for 61 months, and passaged over 300 times. Monolayer-cultured cells were polygonal in shape, showing a pavement-like arrangement and a tendency to pile up without contact inhibition. The epithelial nature of the cultured CUMC-6 cells was confirmed by transmission electron microscopy which demonstrated the presence of desmosomes and tonofilaments. The subcutaneous injection of cultured cells into nude mice gave rise to fast-growing tumors. The transplanted tumor showed similar histological features, but poor differentiation compared to the original tumor. Cultured CUMC-6 cells produced human chorionic gonadotropin beta-subunit (beta-HCG) and alpha-fetoprotein (AFP). Cytosol estrogen and progesterone receptors were not measured in this cell line. The results of isozyme analyses were distinct from the HeLa cell line. Repeated chromosome analysis from passage 6 to 300 revealed that most metaphases of this cell line contained diploid number of chromosomes. The structural abnormality consistently observed in this cell line was the elongation of short arm of chromosome 1. The G- or R-banded pattern of this chromosome suggested inv dup (1) (1pter-->1p34[symbol: see text] 1p21-->1p34[symbol: see text] 1p34-->1qter). Human leukocyte antigen (HLA) typing of CUMC-6 cells indicated the presence of DR12 and DQw3. Analysis of the DNA extracted from the CUMC-6 cells showed the presence of human papillomavirus (HPV) type 16 and 18 DNAs. The results of oncogene analyses using Southern blotting technique revealed amplification and rearrangement of oncogene c-myc and no amplification of oncogene L-myc. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, we have screened CUMC-6 cells for p53 mutation in exons 4 to 9. No mobility shift was observed in this cell line. These results suggest that chromosome 1 abnormality, oncogene alteration, and HPV infection work together in cervical tumorigenesis.
 ...
PMID:CUMC-6, a new diploid human cell line derived from a squamous carcinoma of the uterine cervix. 875 55

Three methods were used in succession to screen a whole adult zebrafish cDNA library for expressed p53-like genes. The sequences of the resultant clones describe an open reading frame 1122 nucleotides in length, with another 43 and 940 bases of 5' and 3' untranslated sequence, respectively. The deduced amino acid sequence of the zebrafish p53 protein is 63% identical to that of trout and 48% identical to that of human p53. Two of the three zebrafish clones overlap to span the entire reported cDNA sequence and are identical in their deduced amino acid sequence over their coincident length. The third clone contains a conservative amino acid change, as well as an inserted amino acid subsequently found to be at the junction of exons 2 and 3, suggestive of alternative splicing in the p53 mRNA for this species. Northern analysis demonstrated a zebrafish p53-related transcript to be present and most abundant in zygotes and early-cleavage embryos less than 1 hour after fertilization, thereafter declining to barely detectable levels at 48 hours. A similar temporal expression was detected for the zebrafish L-myc, known to be present in maternally derived RNA, whereas zebrafish N-myc and the zebrafish homologue of the murine T gene were not detectable prior to the onset of zygotic transcription.
 ...
PMID:Zebrafish (Danio rerio) p53 tumor suppressor gene: cDNA sequence and expression during embryogenesis. 920 Aug 35

104 surgery cases of non-small cell (NSLC) and small cell lung carcinoma (SLC) are studied. Oncoprotein bcl-2 is found in 49 out of 104 (47%) cases, more frequently in SLC (71%) than in NSLC (44%) and this correlated with carcinoma morphological malignancy. L-myc oncoprotein and EGFR were expressed practically in all cases, oncoprotein of the p53 mutated gene in 57% cases. The highest content of p53 was in SLC, large cell and poorly differentiated squamous cell carcinoma. Percentage of cells with mutated p53 statistically correlated with morphological malignancy of lung carcinoma. Oncoprotein of Rb gene was revealed in 51%, most frequently in squamous cell carcinoma (71%) and particularly in its well differentiated types. IGFII was found in 74% NSLC and in 100% SLC with cytoplasmic location in tumor cells; the level of expression was higher in SLC. IGFII 2 and 5 were more frequently observed in the foci of keratinization of squamous cell carcinoma. For the first time IGFP B3 was found not only in the cytoplasm but in the nuclei of tumor cells as well. There was a significant positive correlation between the content of IGFIBP3 in the nuclei of tumor cells and morphological malignancy (poor tumor cell differentiation, larger size and metastases). The mean number of proliferating Ki-67 positive cells was 24% but this figure was much higher (47%) in SLC. Squamous cell carcinoma is characterized by a more frequent and stronger expression of CD44 types 5 and 6 in the cytolemma and this may be considered as a marker of squamous cell differentiation of lung carcinoma.
 ...
PMID:[Immunohistochemistry of biomolecular markers of lung cancer]. 948 14

Pleomorphic adenoma of the lung is a rare neoplasm. Here we describe the first report on oncogenes and tumor suppressor genes in metastasizing pleomorphic adenoma of the lung. A 48-year-old Japanese woman presented with metastasizing pleomorphic adenoma in which both the primary lung tumor and metastatic lesions were composed of benign pleomorphic structures. The mechanism of the metastatic potential was examined by analyzing known oncogenes and tumor suppressor genes by DNA blot analysis and immunohistochemistry. No rearrangements amplifications or overexpressions of oncogenes, bcl-2, c-erbB-2, c-myc, L-myc, N-myc, Ha-ras and Ki-ras were found. In addition, immunohistochemical studies showed no aberrance in expressions of the tumor suppressor gene products, RB, p16 and p53 in the tumor. Some unknown mechanism(s) seems to be responsible for the aggressiveness of this metastasizing pleomorphic adenoma. This mechanism must be elucidated by studies on further case of this rare tumor.
 ...
PMID:A case of pleomorphic adenoma of the lung with multiple distant metastases--observations on its oncogene and tumor suppressor gene expression. 967 59

A new human cancer cell line was established from a metastatic lesion of a small cell lung carcinoma (SCLC-R1) and maintained in continuous culture with a doubling time of 62 h. The SCLC-R1 line, whose ultrastructural features are presented, showed a diploid DNA content, a translocation involving chromosome 16 [t(16;?)(q24;?)] and noticeable deletions in the FHIT (fragile histidine triad) region in the short arm of chromosome 3 [del(3)(p14)] and in the telomeric region of the short arm of chromosome 12 [del(12)(p13)]. The involvement of 12p in metastatic small cell lung cancer is reported here for the first time. No amplification or rearrangements were evident in the c-myc, L-myc, N-myc, int-2, c-erbB-2, H-ras, K-ras, c-mos, and hst-1 genes by Southern blot analysis. Wild-type p53, RB, K-ras and H-ras genes were evident by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. The neuron specific enolase (NSE) level was much higher in the cell line's cytosol than in the patient's serum and the cell line also had high expression of chromogranin A and cytokeratin 19. SCLC-R1 cells were sensitive to cisplatin, carboplatin and doxorubicin. The clinical history of the patient from whom the cell line was derived is reported. The characteristics of this new cell line indicate it to be a useful experimental model to investigate lung cancer biology and anticancer drug response.
 ...
PMID:Chromosomal alterations, biological features and in vitro chemosensitivity of SCLC-R1, a new cell line from human metastatic small cell lung carcinoma. 971 81

p53 monitors genomic integrity at the G1 and G2/M cell cycle checkpoints. Cells lacking p53 may show gene amplification as well as the polyploidy or aneuploidy typical of many tumors. The pathways through which this develops, however, are not well defined. We demonstrate here that the combination of p53 inactivation and c-myc overexpression in diploid cells markedly accelerates the spontaneous development of tetraploidy. This is not seen with either N-myc or L-myc. Tetraploidy is accompanied by significantly higher levels of cyclin B and its associated cdc2 kinase activity. Mitotic spindle poisons accelerate the appearance of tetraploidy in cells either lacking functional p53 or overexpressing c-myc whereas the combination is additive. Restoration of p53 function in cells overexpressing c-myc causing rapid apoptosis, indicating that cells yet to become tetraploid have nonetheless suffered irreversible genomic and/or mitotic spindle damage. In the face of normal p53 function, such damage would either be repaired or trigger apoptotis. We propose that loss of p53 and overexpression of c-myc permits the emergence and survival of cells with increasingly severe damage and the eventual development of tetraploidy.
 ...
PMID:C-myc overexpression and p53 loss cooperate to promote genomic instability. 1002 23


<< Previous 1 2 3 4 Next >>