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)

We have examined expression of the smg p25A (a ras p21-like GTP-binding protein) gene in neural crest-derived tumor cell lines and neuroblastoma tissues. The human neuroblastoma cell lines GOTO, IMR-32, NB-1, and SK-N-SH expressed the 1.6-kilobase smg-25A mRNA. SH-SY5Y and SH-IN, variant cell lines with a neuronal phenotype derived from SK-N-SH, expressed much more smg-25A mRNA than did SH-EP1, a variant line with an epithelium-like phenotype also derived from SK-N-SH. The primitive neuroectodermal tumor cell lines SK-N-MC and KU-SN and the Ewing's sarcoma cell lines RD-ES and SK-ES expressed the smg-25A mRNA to a much smaller extent than did neuroblastoma cell lines. Of 15 human neuroblastoma specimens tested, 13 expressed the smg-25A mRNA to various extents. When the relative ratio of the smg-25A mRNA level to the glyceraldehyde-3-phosphate dehydrogenase mRNA level was compared among neuroblastoma tumor tissues, the value was significantly higher in tumors histologically diagnosed as ganglioneuroblastoma. The smg-25A mRNA was not detected in the tissues of Hodgkin's lymphoma, Wilms' tumor, Ewing's sarcoma, or undifferentiated sarcoma of the liver. These results suggest that the smg-25A mRNA level is closely related to the neuronal differentiation state of tumors derived from the neural crest.
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PMID:Expression of the smg p25A (a ras p21-like GTP-binding protein) gene in human neuroblastoma cell lines and tumor tissues. 212 31

The evidence for human tumor suppressor genes is reviewed. Initial evidence was provided by somatic cell hybridization, where somatic cell hybrids derived from the fusion of malignant and normal parental cells were found to be transformed but nontumorigenic. Tumorigenic segregants appeared at later intervals and were associated with the loss of specific normal chromosomes. Evidence for loss of tumor suppressor genes in many human malignancies was provided by a combination of cytogenetic and restriction fragment length polymorphism analyses. Functional analyses, using monochromosome transfer from normal cells into cancer cells, have confirmed the existence of suppressor genes and their critical role in control of tumor formation. Recently, the tumor suppressor gene Rb-1 has been cloned and also shown to have tumor-suppressing properties. Most recently, a candidate tumor suppressor gene on chromosome 17 (p53) has been implicated in colorectal carcinomas and other human malignancies. It is of interest to note that this gene was originally described as an oncogene. The biological mechanism of tumor suppression has been linked to the induction of differentiation in both somatic cell hybrids and osteosarcoma cells transfected with the normal Rb-1 gene. However, recent studies with monochromosome transfer into neuroblastoma cells indicates that differentiation may be dissociated from tumor suppression. Tumor suppressor genes do not act directly as negative regulators of conventional "dominantly-acting" oncogenes and therefore cannot be considered as anti-oncogenes in the sense of directly interacting with and regulating the expression of such oncogenes as ras and myc. However, it is speculated that they may negatively regulate an, as yet undiscovered, family of oncogenes which would not be dominantly expressed.
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PMID:The evidence for human tumor suppressor genes. 257 36

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

Alterations in the structure and/or expression of oncogenes have been examined to comprehend better the relationship between metastasis and oncogenes. There are reports that amplification and overexpression of N-myc (human neuroblastoma) and erbB-2 (human breast cancer) are closely related to malignant progression. On the other hand, DNA transfer experiments have also been done to assess involvement of oncogenes in metastasis. The active ras oncogenes, which are frequently used, show that transfer of the ras oncogenes endow and/or enhance the metastatic potential of the recipient cells. In addition to the phenomenological studies to determine whether an oncogene alters metastatic potential, increasing attention has been directed to possible phenotypic changes relating to metastasis and affected by oncogenes. It has been clarified that transfer of a certain oncogene, such as ras and fos, alters the expression of biomolecules, for example, metalloproteinases responsible for invasion, autocrine motility factors and cytoskeletal proteins related to cell motility, receptors of fibronectin for cell attachment, and histocompatibility antigens, such as H-2K and H2-D. While further characterization of the biomolecular changes induced by the oncogenes has to be done, the mechanisms of alteration in the expression and function of biomolecules directly involved in the metastatic potential also should be paid attention.
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PMID:[Cancer metastasis and oncogenes]. 267 90

Exposure of neu-oncogene-transformed NIH 3T3 cells to monoclonal antibodies reactive with the neu gene product, p185, results in the rapid and reversible loss of both cell-surface and total cellular p185. Although not directly cytotoxic, monoclonal anti-p185 antibody treatment causes neu-transformed NIH 3T3 cells to revert to a nontransformed phenotype, as determined by anchorage-independent growth. Isotype matched control antibodies of an unrelated specificity do not affect p185 levels or colony formation in soft agar by neu-transformed NIH 3T3 cells. Soft agar colony formation by NIH 3T3 cells transformed by ras oncogenes is not affected by anti-p185 antibody treatment. Anchorage-independent growth of cells from the ethylnitrosourea-induced rat neuroblastoma line in which neu was originally detected by DNA transfection is also inhibited in the presence of anti-p185 monoclonal antibodies. Collectively, these results suggest that p185 is required to maintain transformation induced by the neu oncogene.
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PMID:Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. 286 Sep 72

DNA from human breast carcinoma (SK-BR-3) and neuroblastoma (LA-N-1) cell lines are capable of inducing foci of transformed NIH 3T3 cells after DNA-mediated gene transfer. The blot hybridization analysis of DNA from primary and secondary NIH 3T3 transformants identified additional sequences homologous to the c-Ha-ras 1 oncogene, and revealed amplification of nucleotide sequences homologous to the v-myc oncogene. Restriction fragments of the amplified myc-related sequences correspond to c-myc (SK-BR-3) and N-myc (LA-N-1) loci of the human genome. The results show that active Ha-ras oncogenes can coexist with altered myc oncogenes in breast carcinomas and neuroblastomas. This suggests that a multi-step mechanism involves both ras and myc genes and their cooperation in the development of these tumors.
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PMID:[Activation of ras and myc proto-oncogenes in human breast carcinoma and neuroblastoma]. 302 23

Neuroblastomas represent a spectrum of diseases categorized by histological subtypes, age of the patient, and extent of tumor (stage) at diagnosis. In this study we analyzed Ha-ras p21 (protein with molecular weight of 21,000) expression immunohistochemically on 47 primary human neuroblastomas resected at diagnosis. The data demonstrate that the amount of the Ha-ras product correlates with a favorable prognosis (P less than 0.001) and early stages of disease at diagnosis (P less than 0.05). These findings from unmanipulated human neuroblastomas indicate that the Ha-ras gene product (p21) might play a role in the mechanism(s) controlling aggressiveness in this type of tumor in vivo and that the Ha-ras p21 detected by a simple and reproducible immunohistochemical procedure may be of clinical importance in predicting prognosis in patients with this malignancy.
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PMID:Expression of Ha-ras oncogene products in human neuroblastomas and the significant correlation with a patient's prognosis. 327 97

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

The human B-cell line RJ2.2.5, derived by mutagenesis from a Burkitt lymphoma cell line and selected for loss of HLA class II antigen expression, was infected with recombinant retroviruses containing either the Harvey murine sarcoma virus oncogene v-Ha-ras or the human neuroblastoma homolog NRAS. Both activated ras genes partially complemented the regulatory defect in RJ2.2.5 and specifically increased the expression of the DR and DQ subsets of HLA class II genes. Blot-hybridization analysis and RNase mapping indicated that HLA-DQ alpha-chain mRNA in the infected cell lines was increased to a level at least 50% that of the parent B-cell line, Raji. The levels of HLA-DR and -DQ beta-chain RNA also were increased but to a lesser extent. In contrast, we detected no effect of ras on the quantities of other class II, class I, or invariant-chain mRNAs. Fluorescence-activated cell sorter analysis with antibodies recognizing HLA-DR, -DQ, and class I antigens supported these observations. Enhancement of HLA class II gene expression by ras genes may have important implications for regulation of the immune system in response to transformation.
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PMID:Defective HLA class II expression in a regulatory mutant is partially complemented by activated ras oncogenes. 331 16

It is clear that there are at least two classes of cancer-related genes. The more characterized of these are the oncogenes, whose activation appears to play a major role in human neoplasia. There are now two families of oncogenes, the myc and ras families, whose cooperation seems capable of transforming normal cells in culture to tumorigenic cells. As such, they appear to form complementation groups with immortalizing and transforming properties, respectively. Moreover, the oncogenes can be subclassified as tyrosine kinases or kinase related, GTP binding proteins, growth factors or growth factor receptors or nuclear proteins. More than 20 viral oncogenes have been identified, for which more than 30 proto-oncogenes or pseudogenes exist in the human genome. Many of these have been cloned, characterized to some extent, and mapped to particular chromosomes or regions of chromosomes. Further, more than 20 additional putative oncogenes or transforming genes have been identified by tumor DNA transfection studies or at sites of integration or translocation for which no viral transforming gene cognates exist. Oncogenes can be activated by increased or unregulated expression, increased copy number (duplication, amplification), or somatic mutation resulting in a protein with increased oncogenic potential. Examples of all of these mechanisms can be found in several specific human cancers or leukemias. The cytogenetic correlate of enhanced expression is a translocation between two chromosomes at specific breakpoints with no net loss of genetic material (e.g., increased c-myc expression resulting from the 8;14 translocation in Burkitt's lymphoma). The phenomenon of increased gene copy number can sometimes be visualized as trisomy or tetrasomy for a particular chromosome but more dramatically as the development of extrachromosomal DMs or as chromosomally integrated HSRs (e.g., the N-myc gene amplification seen in neuroblastoma). Finally, certain somatic mutations can be associated with translocations (e.g., the bcr/abl fusion product created as a result of the 9;22 translocation in chronic myelogenous leukemia), but they are more commonly submicroscopic (as characterized by point mutations in the ras gene family). Evidence is accumulating for a second class of cancer-related genes whose absence or inactivation is associated with tumorigenesis. These genes are associated at the cytogenetic level with chromosomal deletions, in which the breakpoints may be variable, but specific, common regions are consistently deleted.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The involvement of oncogenes and suppressor genes in human neoplasia. 331 93


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