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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate whether the presence of an activated ras oncogene influences the ability of tumour cells to metastasize, the c-Ha-ras-1 oncogene cloned from EJ/T24 cells was introduced into MT1 Cl.5/7 mouse mammary carcinoma cells. Since the MT1 Cl.5/7 cells are already tumorigenic but have a low metastatic capacity, this experimental design allows a distinction to be made between the effects of the ras gene on metastasis and tumorigenicity. MT1 Cl.5/7 containing the EJ c-Ha-ras-1 metastasized more readily and to more tissue sites than control cells (2.8 sites/mouse vs 0.9 sites/mouse). The metastases expressed the EJ c-Ha-ras-1 p21 ras proteins; however, one metastasis was discovered that had lost the expression of the c-Ha-ras-1 gene. When these cells were re-tested for metastasis, the rate of metastasis was indistinguishable from that of controls. This observation, coupled with a demonstration that lung colonization potential following intravenous inoculation is unaffected by the presence of the activated ras gene, argues that the effect of mutant ras genes is exerted on the ability of cells to escape from the primary tumour, rather than on a survival in the circulatory systems and ability to seed a second site.
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PMID:Enhanced spontaneous metastasis of mouse carcinoma cells transfected with an activated c-Ha-ras-1 gene. 394 24

Cells in mitosis were found in 51 of 110 (47%) breast tumor samples; karyotypes of nine tumors in the diploid range are presented. The simplest stemline karyotype found was 46,XX, -16, +del(1)(qter----p21). The chromosome homologues most frequently lost were #8, #13, and #16. Monosomy or partial monosomy for chromosome #16 was seen in six cases, including the two simplest and chromosome #16 might be of relevance for initiation of malignant transformation in breast carcinoma. The only chromosome feature common to all nine breast carcinomas was the presence of a marker involving the long arm of chromosome #1, the region shared by all being 1qter----1q21.
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PMID:Cytogenetic analysis in human breast carcinoma. I. Nine cases in the diploid range investigated using direct preparations. 609 7

There is substantial evidence implicating ras genes in a number of human neoplasms. The ras genes of several human tumours display mutational changes which are likely to be responsible for their transforming activity. Normal cells also express ras genes, over-expression of which can induce cellular transformation. ras genes encode proteins of approximately 21,000 molecular weight (MW) (p21) that are localized to the inner surface of the plasma membrane. Much effort is being focused on the elucidation of the physiological function of ras-encoded proteins in normal and transformed cells, concentrating on interactions between p21 and other cellular elements. Recently, Finkel and Cooper reported that p21 in extracts of human bladder carcinoma cells is involved in a molecular complex with the transferrin receptor of these cells. This report aroused considerable interest, particularly as expression of the transferrin receptor has been linked to cell proliferation. I present here evidence that the apparent association of p21 and the transferrin receptor is an artefact of the immunoprecipitation technique.
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PMID:An artefact explains the apparent association of the transferrin receptor with a ras gene product. 609 Sep 54

The EJ bladder carcinoma oncogene is activated by a point mutation in the c-rasH proto-oncogene at the 12th amino acid codon. In an attempt to understand the mechanism of oncogenic activation, a comparative study was undertaken to examine the metabolic turnover and subcellular localization of the p21 protein encoded by the EJ oncogene, the viral oncogene, and its normal cellular homolog. Pulse-labeling experiments indicated that both c-ras p21 proteins were synthesized by a very similar pathway, as was observed for the viral p21 protein of Harvey murine sarcoma virus. The pro-p21 proteins were detected in free cytosol, and the processed products were associated with plasma membrane. The intracellular half-life of p21 proteins was determined by pulse-labeling and chasing in the presence of excess unlabeled methionine. Although both p21 proteins of EJ and the normal c-ras genes which are not phosphorylated have a half-life of 20 h, the viral p21 protein of Harvey murine sarcoma virus which includes a phosphorylated form is much more stable in cells, having a half-life of 42 h, apparently due to phosphorylation.
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PMID:Metabolic turnover of human c-rasH p21 protein of EJ bladder carcinoma and its normal cellular and viral homologs. 609 27

A possible causal association between chromosome structural change and neoplastic transformation has long been mooted, particularly since chromosomal changes occur frequently in the cells of a variety of malignancies. Only in recent years, however, has the evidence in support of this contention begun to appear convincing, and this has followed from the application of developments in cytogenetic techniques. The advent of methods for revealing specific bands in the human metaphase complement has enabled all the chromosomes and many chromosomal regions to be unambiguously identified, and the recent application of prophase banding methods gives further improvements in resolution. With these techniques, specific constitutional chromosomal deletions or translocations have been discovered in inherited cases of retinoblastoma (del.13q14), Wilms' tumour with aniridia (del.11p13) and renal-cell carcinoma (t(3:8) (p21:q24)), in which each of the chromosomal changes appears to be a dominant factor in inheriting a predisposition to a tissue-specific tumour. A heritability for cancer predisposition is also associated with the inherited chromosomal instability syndromes of Bloom's, Fanconi's anaemia and ataxia telangiectasia, although specific chromosomal changes have not been reported to be associated with the neoplasms in such individuals, except in some cases of lymphoma and leukaemia in ataxia telangiectasia. Specific chromosomal translocations have, however, been recorded in a variety of malignancies, with a particular involvement of chromosomes 22, 14, 8, 15, 17 and 21. However, although many hundreds of patients with the specific 9/22 rearrangement seen in chronic myeloid leukaemia and also those with the 14/8 rearrangement in Burkitt's, and other, lymphomas have been described, no single case in which these rearrangements were present as constitutional changes has been reported. The possible nature of the changes seen at the cytogenetic level in terms of gene content of the chromosomes involved is discussed.
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PMID:Cytogenetics of heritability in cancer. 629 35

More than 10 different dominant transforming genes (oncogenes) have been identified in human tumours. A human bladder carcinoma oncogene, closely related in sequence to retroviral transforming genes, is split into four exons; the first encodes the N-terminal 37 residues of p21, a protein of unknown function. The oncogene is activated by a single point mutation (guanine to thymine) resulting in the change glycine to valine at position 12 of p21 (refs 3, 4). We report here that the amino acid sequence surrounding this residue is highly homologous to the beta-subunit of mitochondrial and bacterial ATP-synthase in the region of the polypeptide that is believed to contribute to nucleotide binding. Thus, p21 may form part of an enzyme that uses purine nucleotides in catalysis. This is consistent with the finding that an equivalent murine oncogene product binds GTP.
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PMID:Homology between human bladder carcinoma oncogene product and mitochondrial ATP-synthase. 629 96

We have molecularly cloned and sequenced cDNA to the transcript of H-ras-1, the transforming gene of the T24 human bladder carcinoma cell line. The transcript derives from at least five exons in the H-ras-1 gene, and RNA splicing occurs at sites typical of exon-intron junctions. T24 H-ras-1 RNA has an AUG-initiated open reading frame of 567 nucleotides, which can encode a protein of mass comparable to the apparent molecular weight of the T24 H-ras-1 gene product. The T24 H-ras-1 gene product is nearly identical to v-H-ras p21, the transforming protein encoded by the genome of Harvey sarcoma virus. We discuss the implications of this sequence conservation in the structure-function relationships of ras proteins.
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PMID:Sequence and structure of the coding region of the human H-ras-1 gene from T24 bladder carcinoma cells. 630 18

It has been recently shown that malignant activation of the c-has/bas proto-oncogene in T24 human bladder carcinoma cells was mediated by a single point mutation. A deoxyguanosine located at position 35 of the first exon of this proto-oncogene was substituted by thymidine. These findings predicted that the resulting oncogene would code for a structurally altered p21 protein containing valine instead of glycine as its 12th amino acid residue. We now report the spontaneous activation of the human c-has/bas proto-oncogene during transfection of NIH/3T3 cells. As in T24 cells, this in vitro activated oncogene also acquired malignant properties by a single point mutation. In this case we have detected a G leads to A transition, which occurred at the same position as the mutation responsible for the activation of the T24 oncogene. These results predict that the p21 protein coded for by the spontaneously activated c-has/bas gene will incorporate aspartic acid as its 12th amino acid residue. Computer analysis of the secondary structure of c-has/bas encoded p21 proteins indicates that substitution of the glycine residue located at position 12, not only by aspartic acid or valine but also by any other amino acid, would result in the same structural alteration. These findings indicate that a specific conformational change is sufficient to confer transforming properties to this p21 protein. Moreover, they predict that any mutation affecting the coding properties of the 12th codon of the c-has/bas proto-oncogene will lead to its malignant activation.
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PMID:Spontaneous activation of a human proto-oncogene. 630 40

DNAS of some human tumours can transform NIH 3T3 fibroblast cells, thus demonstrating the transforming potential of human ras genes (Hu-rasHa, Hu-rasKi, and Hu-rasN, respectively Harvey, Kirsten and neuroblastoma ras genes). Only a small percentage of a given type of human carcinoma, however, scores positive in this assay system. Activation of ras and subsequent transformation of NIH 3T3 cells are either by a point mutation in the ras gene or enhanced expression of the normal, or proto-onc, ras gene. If the transformation of a given human tumour involves the enhanced expression of the normal or cellular ras gene and the resulting gene product, the tumour DNA would probably score negative in the NIH 3T3 transfection assay. In human colon carcinoma, for example, lesions at position 12 of Hu-rasKi have been found. None of nine colon carcinomas obtained at biopsy, however, contain the ras lesion at this position, using a Hu-rasHa probe; one other colon carcinoma does appear to contain amplified proto-onc ras, and other colon carcinomas do have increased levels of ras RNA. There are at least three explanations for these observations. Either very few colon carcinomas contain point-mutated ras, the lesion in the majority of colon carcinomas is at a position other than 12 or ras activation in many colon carcinomas involves the enhanced expression of either the point-mutated or proto-onc form of a ras gene. We have now used monoclonal antibodies directed against a synthetic peptide reflecting sequences of the human T24 ras gene product to define ras p21 protein expression in a spectrum of colonic disease states. Immunohistochemical analyses of individual cells within tissue sections reveal differences in ras p21 expression in colon carcinomas compared with normal colonic epithelium, benign colon tumours and inflammatory or dysplastic colon lesions. Our data suggest that ras p21 expression is correlated with depth of carcinoma within the bowel wall, and is probably a relatively late event in colon carcinogenesis.
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PMID:Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases. 648 68

Alteration in gene structure has been shown to occur in some human tumours. These altered genes, termed oncogenes, were originally identified by their ability to induce foci of transformed cells on transfected mouse 3T3 cultures. The oncogene identified in the EJ/T24 human bladder carcinoma is similar to the transforming gene of BALB and Harvey murine sarcoma virus (MSV) and differs from its counterpart in normal cells by a single amino acid. All three of these Ha-ras genes direct the production of similar proteins (p21). While the ras gene appears to be involved in tumour formation in some situations, its role is unclear. The ras protein product (p21) binds guanine nucleotides and has a unique autophosphorylating activity, but no other enzymatic activity has been found. We report here the injection of purified Ha-ras p21 protein, made in Escherichia coli from the gene of BALB-MSV, into NIH 3T3 cells and show that the purified protein itself is sufficient to induce a transformed morphology. In addition, the injected protein stimulates quiescent cells to enter the S-phase of the cell cycle. This result clearly demonstrates that the ras gene functions directly through the protein product. It also establishes an assay for the protein which depends on its activity within a living cell. The transforming activity of a p21 ras protein equivalent to the product of the normal cellular ras gene, is also demonstrated.
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PMID:Transformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein. 661 9


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