Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The genetic events involved in the development of metastases of epithelial ovarian cancer are largely unknown. One gene postulated to play a role in tumour metastasis suppression is NME1 (nm23-H1), and an inverse relationship between NME1 expression and metastatic potential has been observed for some solid tumours. In this study we have investigated the levels of mRNA expression of the 2 isoforms of the NME gene, NME1 and NME2. A maximum of 45 tumours samples from 33 patients were available for Northern blot analysis. We observed variable levels expression of NME1 and NME2 mRNA. The average level of NME1, but not NME2, mRNA expression was statistically higher in metastatic biopsies when compared with primary tumour biopsies. To examine the possible tumour suppressor gene role of NME1 in ovarian tumours, 76 patients were investigated by Southern blot analysis to determine the rate of allelic deletion. Allele loss at 5 other chromosome 17 loci (D17S5, TP53, NF1, D17S74, D17S4) was also evaluated for many of these 76 patients. Allele loss was observed in 22/30 (73%) informative patients at the NME1 locus. We also observed high rates of allele loss at the other loci evaluated. No correlations with clinical stage, histological subtype or patient survival were observed in either mRNA or DNA analyses. We have established that tumour progression in ovarian cancer is accompanied by over-expression of the NME1 gene; however, despite high rates of allele loss at the NME1 locus, the concept that NME1 may be a candidate tumour suppressor gene in ovarian cancer cannot be confirmed by this study.
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PMID:Increased expression of the NME1 gene is associated with metastasis in epithelial ovarian cancer. 762 7

An immortal cell line was established by transfecting a myc oncogene into rat embryo cells (REC:myc). This cell line was diploid, contact inhibited and grew well in culture. Exposure to a single 200 cGy dose of 6 MeV alpha-particles transformed these cells with a frequency of focus formation of approximately 3.6 x 10(-4) compared with a transformation frequency of < 7.8 x 10(-6) for primary cultures of REC. Isolates of alpha-particle-induced REC:myc (REC:myc:alpha) foci displayed anchorage-independent growth in soft agar and were tumourigenic in nude mice. Molecular studies demonstrated no alteration of gene structure or expression of the transfected or of the endogenous c-myc genes. Similarly, there was no alteration of the structure of Ha-ras, Ki-ras, or N-ras. The expression of Ha-ras, Ki-ras, N-ras and raf was not altered significantly. Assay for dominant oncogenes via DNA-mediated gene transfer into NIH3T3 cells was positive for nine of 13 REC:myc:alpha transformants. All NIH3T3 isolates contained bands hybridizing to rat repetitive DNA. NIH3T3 transformants from a tertiary round of transfection were analysed by Southern blot analysis for the presence of Ki-ras, N-ras, raf, trk, abl, fms, src, mos, fos, sis, fps, erbA, erbB or neu oncogenes of REC origin, and none were detected. Tertiary NIH3T3 transformants from three REC:myc:alpha transformants contained bands corresponding to Ha-ras but no point mutations were identified at the known hotspots of exons 1 or 2 of the donor REC:myc:alpha transformants. The inactivation of the tumour suppressor genes Rb, and p53, and the anti-metastasis gene, nm23, was evaluated by Southern and Northern hybridization analysis. Southern blots demonstrated that at least one allele of Rb, p53 and nm23 was present and no large scale structural changes were detected. No expression of Rb or p53 was detected in REC:myc or the alpha-particle-induced REC:myc transformants. The expression of nm23 was not altered in the transformed cell lines. While the analysis of the role of tumour suppressor gene inactivation in radiation-induced cell transformation is only in the initial stages, the results of DNA-mediated gene transfer into NIH3T3 cells suggest that unidentified dominant oncogenes are associated with alpha-particle-induced transformation in vitro.
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PMID:Molecular analysis of rat embryo cell transformants induced by alpha-particles. 790 39

We used Southern blot analysis and polymerase chain reaction-based techniques to examine deletions of tumour suppressor gene loci in 91 primary colorectal tumours. The tumour suppressor genes studied were MCC and APC on chromosome 5q, p53 on chromosome 17p, DCC on chromosome 18q, and the putative suppressor gene nm23-H1 on chromosome 17q. The most frequent allelic loss observed was in chromosome 17p with 76% (68/89) of informative tumours showing loss of heterozygosity at this locus, followed by 34% (19/55) for DCC, 31% (12/39) for MCC, 17% (9/53) for APC and 16% (3/19) for nm23. No significant differences in the frequency of these suppressor gene allelic losses were observed between Dukes B and C stage adenocarcinomas.
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PMID:Loss of heterozygosity of tumour suppressor gene loci in human colorectal carcinoma. 808 Jun 84

An inverse correlation has been demonstrated between nm23 gene expression and metastasis. The gene is located on chromosome 17q (q1.1-q2.1), a region distinct from tumour suppressor gene p53. We have previously reported expression of mutant products of p53 gene to be significantly associated with worsening degrees of differentiation in squamous cell carcinoma. nm23 gene product, which shows complete identity to human erythrocyte nucleoside diphosphate kinase, was used to raise an affinity-purified polyclonal antibody Ab-11 which is applicable to formalin-fixed and paraffin-embedded tissues. Keratoacanthomas and squamous cell carcinomas of the epidermis form a fascinating human tumour model in which to test the hypothesis that the nm23 gene confers 'anti-metastatic' properties, since the former never metastasise while the latter have this potential. Two observers rated immunohistochemistry for the nm23 gene product as the proportion of tumour positive from grades 1-4 (corresponding to 25, 50, 75 and 100% of tumour cells stained). Nineteen typical keratoacanthomas, 20 well, 21 moderately and 8 poorly differentiated epidermal squamous cell carcinomas were studied. The Jonckheere-Terpstra test statistic of association between staining grade and lesion type was 762.5, p = 0.189 (2 tails), p = 0.0945 (1 tail). There was no statistically significant trend in tumour staining from keratoacanthoma through decreasing grades of differentiation of squamous cell carcinoma. nm23 product expression does not appear to correlate with differentiation, itself an indicator of metastatic potential, in this system of human squamous cell neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:'Anti-metastatic' nm23 gene product expression in keratoacanthoma and squamous cell carcinoma. 835 13

We have examined 41 cases of follicle centre cell lymphoma with fluorescent PCR of microsatellite repeats closely linked to or within six tumour suppressor gene loci (APC, DCC, P53, RB1, WT1 and NM23). These probes are highly informative with heterozygousity rates in the range of 57%-90%. In addition we have used four loci from chromosome 6 (D6S260, TNFa, D6S281 and D6S262) as control loci which are unlikely to be involved in the pathogenesis of lymphoma. Of 369 informative PCR reactions allele imbalance was identified in 38 (10%) and this was seen in 23 of the 41 cases. Looking at individual loci allele imbalance was seen in APC(1) 11%, APC(2) 12%, P53(1) 5%, P53 (2) 7%, WT1 5%, RB1 13%, DCC 18% and NM23 0%. This frequency of change was no different from that seen at the control loci D6S260 16%, TNFa 20%, D6S281 4% and D6S262 9%. In the indolent phase of germinal centre cell lymphoma there is therefore quite a high rate of allele imbalance at all loci but this is no higher in those loci linked to tumour suppressor genes.
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PMID:Allele imbalance at tumour suppressor loci during the indolent phase of follicle centre cell lymphoma. 872 37

Whilst tumour thickness is of great value in predicting prognosis for groups of patients in different categories, it is of less value for individual patients. It has been proposed that expression of the nm23 gene, a putative tumour suppressor gene, is associated with improved outcome in a number of human neoplasms including malignant melanoma. We assessed nm23 expression in 22 patients who had primary melanomas > 3mm thick. Ten have survived to date and 12 died of melanoma. Using immunohistochemical methods, we found no significant differences in gene expression between the two groups.
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PMID:The value of Nm23 expression as an independent prognostic indicator in primary thick melanoma. 886 22

An inverse correlation between the nm23 RNA level and tumour progression of melanocytes has been reported. To elucidate whether the expression of nm23 gene product in malignant melanoma is also inversely correlated with metastatic potential, conventional prognostic parameters or the tumour suppressor protein p53, immunohisto-chemical studies using a monoclonal antibody against nm23-H1 protein were performed on 138 benign and malignant melanocytic tumours. The expression of nm23 protein was compared with that of p53 protein and conventional clinicopathological prognostic factors. The nm23 protein level in benign melanocytes and metastatic melanoma cells was also studied by Western blot analysis. No significant difference regarding the protein was observed between naevi and melanomas, either at histological or protein levels. The expression correlated with local recurrence within 1 year after surgery, level of invasion and tumour thickness, but no parallels were observed between the nm23 and p53 proteins, suggesting that gene is regulated by independent mechanisms, although located on the same chromosome. There was no inverse correlation between the nm23 protein and melanoma metastasis which suggested that the nm23 protein does not appear to be lost during melanoma metastasis.
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PMID:Expression of metastasis suppressor gene product, nm23 protein, is not inversely correlated with the tumour progression in human malignant melanomas. 897 56

Tumour suppressor genes and oncogenes that control proliferation and apoptosis are known to play an important role in embryogenesis, second trimester fetal oocyte loss, adult ovulation, and in adult male testicular degeneration. We have examined tumour suppressor genes, oncogenes and oestrogen receptors during first trimester human gonadal differentiation to investigate their role at this crucial phase in development. Immunohistochemistry was used to localize the gene products of Bcl-2, c-erB-2, c-myc, p53, nm23 and oestrogen receptor. As gonadal development occurred at 6-12 weeks gestation, a changing pattern of expression was observed that varied in different cell types. The oestrogen receptor was not present in oogonia, spermatogonia and supporting cells during the first trimester. This study highlights the importance of oncogenes and tumour suppressor genes in first trimester gonadal development.
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PMID:Oncogenes and tumour suppressor genes in first trimester human fetal gonadal development. 1042 1

Because plants are sessile, they have developed intricate strategies to adapt to changing environmental variables, including light. Their growth and development, from germination to flowering, is critically influenced by light, particularly at red (660 nm) and far-red (730 nm) wavelengths. Higher plants perceive red and far-red light by means of specific light sensors called phytochromes(A-E). However, very little is known about how light signals are transduced to elicit responses in plants. Here we report that nucleoside diphosphate kinase 2 (NDPK2) is an upstream component in the phytochrome signalling pathway in the plant Arabidopsis thaliana. In animal and human cells, NDPK acts as a tumour suppressor. We show that recombinant NDPK2 in Arabidopsis preferentially binds to the red-light-activated form of phytochrome in vitro and that this interaction increases the activity of recombinant NDPK2. Furthermore, a mutant lacking NDPK2 showed a partial defect in responses to both red and farred light, including cotyledon opening and greening. These results indicate that NDPK2 is a positive signalling component of the phytochrome-mediated light-signal-transduction pathway in Arabidopsis.
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PMID:Phytochrome signalling is mediated through nucleoside diphosphate kinase 2. 1052 31

Bladder cancer is clinically characterized by a high recurrence rate for superficial tumours up to 70% and by the invasiveness of advanced bladder cancer. To learn more about the biological behaviour of an individual bladder cancer different tumour markers have been investigated. The aim of our study was to compare the potential of aggression of both superficial and invasive bladder tumours by means of the proliferation marker Ki67, the tumour suppressor gene p53, the non metastasizing protein nm23 and the evaluation of DNA ploidy. We examined 36 patients, 28 with a bladder tumour (Ta-T4) and 8 without as a control group. For immunohistochemistry (Ki67, p53, nm23) we took paraffin sections and scored semiquantitatively under a microscope. The DNA cytophotometry was done on bladder washings by evaluating the DNA ploidy of single cells. The results showed that benign tissues were negative for Ki67 and p53 but positive for nm23. The DNA diagnosis was diploid for all benign samples. The superficial bladder cancer (Ta, T1) showed, in comparison to the invasive tumours, significantly lower numbers of aneuploid cells and a higher rate of p53 mutations. On the other hand the invasive tumours (T2-4) were correlated to significantly higher proliferation rates and higher potencies for metastasizing. The combination of the investigated tumour markers allowed a graduation of the biological behavior of an individual bladder cancer. Especially a high p53 mutation rate and a non aneuploid DNA diagnosis were indicators for the recurrence of superficial bladder tumours. Invasive growth of bladder cancer was characterized by high Ki67 proliferation and low nm23 protein binding.
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PMID:Immunohistochemical examinations (Ki67, p53, nm23) and DNA cytophotometry in bladder cancer. 1132 61


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