Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the potential role of the ras protooncogene proteins in a specific tissue, the present study determined the levels of individual c-ras-encoded p21 proteins in the rat ovary during various stages of physiological function. p21 protein was extracted from ovaries taken from immature normal female rats, mature nonpregnant animals in the metestrus stage of the estrus cycle, rats at various stages of pregnancy, and actively lactating animals. Levels of individual p21s were evaluated by immunoblot analysis with specific antibodies to the p21 proteins encoded by the Kirsten, Harvey, and neuroblastoma c-ras protooncogenes, c-Ki-ras, c-Ha-ras, and N-ras. Results showed that c-Ki-ras p21 is at its lowest level in the immature ovary and increases with development of the corpora lutea to its highest levels at day 16 of pregnancy, after which levels decline and then rise again during lactation. This pattern, which mimics that of circulating progesterone levels, suggests that ovarian c-Ki-ras p21 levels are regulated and that c-Ki-ras p21 plays a role in the differentiated function of the rat ovary, likely the luteal compartment. In contrast, levels of c-N-ras p21 did not appear to vary with changes in the physiological function of the ovary but appeared to be constitutive. A preferential role for the c-Ki-ras p21 may be due to the documented unique differences in the structure of the carboxyl terminus of this particular c-ras p21.
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PMID:Ovarian expression of cellular Ki-ras p21 varies with physiological status. 157 Mar 48

Little is known about the prevalence and significance of ras gene activation in neural crest tumors such as neuroblastomas, pheochromocytomas, and medullary thyroid cancers (MTCs). Therefore, we analyzed DNA from 10 human neuroblastoma cell lines and 10 primary human pheochromocytomas for activating mutations in N-ras, H-ras, and K-ras. We also studied DNA from 24 primary neuroblastomas and 10 MTCs for N-ras mutations. ras genes were analyzed by direct sequencing of specific DNA fragments amplified by the polymerase chain reaction. With the exception of the SK-N-SH cell line, the examined ras gene sequences were normal in all the neuroblastomas, pheochromocytomas, and MTCs tested. A single point mutation was identified at codon 59 (GCT(ala)----ACT(thr)) in one N-ras allele in an SK-N-SH subline. Interestingly, this mutation is different from the activating codon 61 mutation which resulted in the initial identification of N-ras from SK-N-SH DNA. Therefore, we analyzed the sequences of earlier passages and sublines of the SK-N-SH cell line, but mutations at codon 59 or 61 were not detected, suggesting that neither mutation was present in the primary tumor. Our results indicate that N-ras mutations may occur spontaneously during in vitro passage of cell lines but rarely, if ever, occur in primary neuroblastomas, pheochromocytomas, and MTCs. In addition, we have not found H-ras or K-ras mutations in any neuroblastoma cell line or primary pheochromocytoma.
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PMID:Low frequency of ras gene mutations in neuroblastomas, pheochromocytomas, and medullary thyroid cancers. 199 49

Neuroblastoma may arise from the blockage of differentiation of neuroblast along the neuronal pathway. In previous studies, we were able to induce differentiation of certain neuroblastoma cell lines with NGF. In order to study the gene regulation during differentiation, we hybridized several cDNA probes with RNA extracted from different cell lines before and after NGF treatment, and found that c-myc oncogene was down-regulated in NGF-induced differentiated cells in comparison with the control samples. The time course of c-myc down-regulation was concordant with the appearance of morphological changes of differentiation. No significant change was found in the expression of other oncogenes like K-ras and N-ras in the neuroblastoma cell lines before and after NGF treatment. The results indicate that down-regulation of c-myc oncogene may be one of the important events during NGF-induced differentiation and over expression of c-myc oncogene may, at least partly, be responsible for the development of neuroblastoma.
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PMID:[Gene regulation during NGF--induced differentiation of neuroblastoma cells]. 206 83

Cellular oncogenes appear to be involved in the control of normal cell growth and differentiation. The abnormal activation of these genes in naturally occurring and experimentally induced cancers may have an important role in the expression of the malignant phenotype in cancer cells. Mechanisms for the activation of these genes include chromosomal translocation, point mutation, and DNA amplification. The amplification of specific oncogenes correlates with clinical prognosis in several human malignancies, including breast cancer and neuroblastoma. We examined 21 fresh-frozen human squamous cell carcinomas of the aerodigestive tract for amplification of 10 known cellular oncogenes (c-myc, N-myc, L-myc, N-ras, H-ras, K-ras, erb-B, erb-B2, raf, and int-2), using Southern blotting techniques. Eleven of 21 tumors demonstrated a two-fold to 11-fold amplification of the int-2 oncogene, one member of a family of genes related to basic fibroblast growth factor. Amplification of c-myc, a gene that codes for a DNA-binding protein involved in the regulation of cell growth, was seen in two tumors. None of the other eight genes studied were amplified in any of the tumor specimens.
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PMID:Oncogene amplification in squamous cell carcinoma of the head and neck. 224 38

The effect of the N-ras oncogene on the propensity of transformed cells to disseminate from the tumor and to metastasize, using NIH 3T3 cells transformed either with human melanoma DNA containing the N-ras oncogene or with the cloned N-ras from human neuroblastoma, was investigated. The results show that NIH 3T3 expressing these genes readily formed tumors after subcutaneous injection in nude mice. Spontaneous lymph node metastasis was observed after a first cycle of transfection in one animal inoculated with cells containing human melanoma N-ras oncogene, and in 95 per cent of the animals after the second and third rounds of transfection, indicating that the metastatic capacity was transferred. In all cases human N-ras oncogene was found in both the metastases and the associated tumors. No control NIH 3T3 cells formed tumors or metastases in nude mice, and NIH 3T3 cells transfected with cloned N-ras activated oncogene formed tumors in 100 per cent of injected mice, but no spontaneous metastases. Thus human activated N-ras gene may not be sufficient to confer metastatic behavior in nude mice and the metastatic ability of human melanoma DNA transfected cells may be due to, among other possibilities, expression of other gene sequences from melanoma DNA co-transfected with the N-ras oncogene, or to specific activated murine sequences switched on during the initial process of transfection.
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PMID:Transformed NIH 3T3 cells expressing human melanoma N-ras oncogene metastasize to lymph node in nude mice. 265 Sep 39

Two new neuroblastoma cell lines, KG-MH and KM-YH have been established from fresh tumour samples. In vitro growth characteristics are presented together with a karyological analysis. Northern and Southern blot experiments have been performed using molecularly cloned probes for c-myc, N-myc, c-Ha-ras, c-Ki-ras, and N-ras oncogenes. Both cell lines showed expression for N-myc, while c-myc expression was not detected. Cell line KM-YH, with a rather long population doubling time of 78 h, showed additional expression for the three ras genes.
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PMID:Expression of myc and ras oncogenes in two newly established neuroblastoma cell lines. 266 22

Fifteen primary neuroblastomas and four bone marrow samples from neuroblastoma patients, representing clinical Stages I to IV, have been screened for mutations in codons 12, 13, and 61 of N-ras. Neuroblastoma DNAs were subjected to the polymerase chain reaction to amplify the relevant sequences and were then hybridized with specific oligonucleotides to locate and identify point mutations. The results show that one Stage I tumor contained an N-ras gene that was activated by a GC-CG transversion of the first base of codon 61, while in one Stage II tumor, activation of N-ras involved a GC-CG transversion of the first position of codon 13. N-ras activations were not detected in the six Stage III tumors and eight Stage IV tumors that were examined.
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PMID:Activated N-ras oncogenes in human neuroblastoma. 267 45

Using a rapid dot-blot screening procedure based on DNA amplification and hybridization to synthetic oligonucleotide probes, we investigated 18 neuroblastomas in various clinical stages for the presence of ras mutations. In none of the samples was a mutation in the relevant codons 12, 13 or 61 of Ha-ras, Ki-ras or N-ras found. These data virtually exclude the participation of mutated ras genes in the genesis of neuroblastoma.
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PMID:Incidence of ras gene mutations in neuroblastoma. 329 51

A molecular clone containing part of the transforming gene from two human sarcoma cell lines, HT1080 and RD, has been obtained and shown to represent a new member of the human ras gene family. The transforming gene has undergone no major rearrangements and has not been amplified in either sarcoma cell line. The major transcript from the gene is 2,200 nucleotides long and is present at the same levels in both normal fibroblasts and tumour cells. The same gene is also activated in HL60, a promyelocytic leukaemia line and in SK-N-SH, a neuroblastoma line. The gene, N-ras, is located on chromosome 1.
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PMID:Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. 630 21

Three distinct transforming genes present in human tumor cell lines are all related to the viral oncogenes of Harvey and Kirsten murine sarcoma viruses, designated v-H-ras and v-K-ras, respectively. The transforming gene of a bladder carcinoma cell line has been shown to be a human homolog to v-H-ras [Parada, L. F., Tabin, C. J., Shih, C. & Weinberg, R. A. (1982) Nature (London) 297, 474-478; Santos, E., Tronick, S. R., Aaronson, S. A., Pulciani, S. & Barbacid, M. (1982) Nature (London) 298, 343-347]. The transforming gene common to one colon (SK-CO-1) and two lung carcinoma (SK-LU-1 and Calu-1) cell lines is the same human homolog of v-K-ras as is the transforming gene previously identified in a lung carcinoma cell line Lx-1 [Der, C. J., Krontiris, T. G. & Cooper, G. M. (1982) Proc. Natl. Acad. Sci. USA 79, 3637-3640]. The transforming gene of SK-N-SH neuroblastoma cells is weakly homologous to both v-H-ras and v-K-ras. NIH 3T3 cells transformed with the SK-N-SH transforming gene contain increased levels of a protein serologically and structurally related to the protein products of the v-H-ras and v-K-ras genes. Therefore, it represents a third member of the ras gene family, which we have called N-ras. Based on the homology with the v-ras genes, we have established the orientation of transcription and approximate coding regions of the cloned human K-ras and N-ras genes.
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PMID:Three human transforming genes are related to the viral ras oncogenes. 657 64


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