Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transfection of the oncogene encoding the nuclear protein p53 into a low-metastatic mouse carcinoma cell line resulted in enhanced metastatic capabilities in clones that showed increased p53 protein expression [Pohl J, Goldfinger N, Radler-Pohl A, Rotter V, Schirrmacher V (1988) Mol Cell Biol 8:2078-2081]. This effect seemed neither to be due to increase in cytoplasmic diacylglycerol levels nor to reduced cell-surface expression of class I major histocompatibility antigens.
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PMID:Induction of the metastatic phenotype by transfection of the nuclear oncogene p53: increases in cytoplasmic diacylglycerol levels and reduction in class I major histocompatibility antigen expression are not sufficient to explain the changes in metastatic capacities. 265 33

Amplification of the c-myc gene has been frequently reported in breast carcinomas. However the precise function of the c-myc protein is still unknown and the nature of the selective advantage offered to a cell by an overexpression of such a protein is unclear. We are addressing this question using the SW 613-S human breast carcinoma cell line as a model system. This cell line harbours an amplified c-myc gene and a mutated c-Ki-ras gene. By various criteria the amplified c-myc gene of SW613-S cells appears undistinguishable from a normal human c-myc gene. The SW613-S cell line is heterogeneous: it contains cells with a high level of amplification and carrying the extra copies of the c-myc gene in double minute chromosomes (DMs) and cells with few c-myc genes integrated into chromosomes. DM-containing cells are progressively lost upon in vitro cultivation but are selected for during in vivo growth, as tumors in nude mice, or by cultivating the cells in a chemically defined, serum-free medium or under conditions preventing anchorage. Clones with different levels of amplification and different chromosomal localization of the c-myc copies were isolated from the SW 613-S cell population. Those with a high level of amplification and expression of the c-myc gene are tumorigenic in nude mice, whereas those with a low level are not. Introduction of c-myc gene copies by transfection confers tumorigenicity to the nontumorigenic clones, indicating that a high level of amplification of the c-myc gene contributes to the tumorigenic phenotype of SW 613-S cells. Tumorigenic clones grow unattached, are able to proliferate in a chemically defined medium, and produce high levels of several growth factors (e.g. TGF-alpha, IGF2). Nontumorigenic clones are more dependent upon anchorage for growth, show a restricted growth in defined medium, and produce low or undetectable level of the growth factors tested. We have identified several genes, besides c-myc, the expression level of which is markedly different in the two types of clones. TGF-alpha, IGF2, PDGF-A, int-2, cytokeratins K8 and K18 and ferritin H chain are overexpressed in tumorigenic clones. In contrast, c-erbB1 (EGF receptor), c-jun, vimentin and p53 are expressed at a higher level in the nontumorigenic clones. Finally the major histocompatibility class I antigens, ferritin L chain, TGF-beta and c-Ki-ras, are examples of genes expressed at the same level in both types of clones.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The human breast carcinoma cell line SW 613-S: an experimental system to study tumor heterogeneity in relation to c-myc amplification, growth factor production and other markers (review). 268 29

An autopsy case of HTLV-I associated myelopathy (HAM) was reported. The patient was a 55-year-old man from Kagoshima, who had no history of blood transfusion. He was admitted to our hospital because of muscle weakness of legs and dysuria, which having since one month ago. On admission, he was able to walk with assistance, but his legs were severely spastic, and Babinski's sign was positive bilaterally. Superficial sensation was normal, but vibration sense was mildly decreased in his legs. CSF showed mild mononuclear pleocytosis with elevated protein. Myelogram and CT were normal. Serum and CSF antibodies to HTLV-I were positive at titers of X4,096 and X128, respectively by immunofluorescent assay, and specific IgG bands (p19, p24, p28 and p53 in serum and p19, p24, p53 in CSF) were detected by western blot analysis. His paraparesis continued to worsen. He became bed-ridden within 2 months. He was received corticosteroid medication. He regained the ability to walk with assistance, and continued taking corticosteroid. In July 4, 1986, macrohematuria appeared and inoperable transitional cell carcinoma of rt. kidney was found by further examination. Chemotherapy were not effective against the carcinoma and he died on July 21, 1987. Neuropathological findings were summarized as follows: cerebral hemisphere was normal except for mild cellular infiltration in the leptomeninges; lesions consisted in unilateral pyramidal tract of pons & medulla and in partial anterior, posterior and lateral columns of the spinal cord; demyelination with axonal degeneration, marked gliosis, numerous lipid-laden macrophages and mild perivascular infiltration of mononuclear cells in these areas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An autopsy case of HTLV-I associated myelopathy (HAM)]. 275 64

We have investigated the possibility that structural alterations of the 'nuclear' oncogene family (c-myc, N-myc, L-myc, fos, myb and p53) leading to aberrant expression might, as in several other tumour types, play a role in the multi-stage development of tumorigenesis in the human thyroid follicular cell. Direct analysis of expression by slot and Northern blot RNA hybridisation showed that normal thyroid expresses surprisingly high levels of fos, and to a lesser extent c-myc, c-myc expression was markedly increased in all tumours, both benign and malignant, but no increase was seen in any other nuclear oncogene. fos expression was reduced specifically in one type of malignant tumour-follicular carcinoma-in inverse correlation with differentiation. Southern blot analysis showed no evidence of rearrangement or amplification of c-myc, or of any other 'nuclear' oncogene in any thyroid tumour. We conclude that there is no evidence that a primary abnormality of these genes plays a role in thyroid follicular cell tumorigenesis and suggest that the observed changes in expression can be adequately explained as secondary consequences of the tumour phenotype.
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PMID:Structure and expression of nuclear oncogenes in multi-stage thyroid tumorigenesis. 280 26

Human p53 gene was cloned from the normal human placenta DNA and DNA from the strain of human kidney carcinoma transplanted into nude mice. Representative gene library from tumor strain of human kidney carcinoma and library of 15 kb EcoRI fragments of DNA from normal human placenta were constructed. Maniatis gene library was also used. Five clones were isolated from kidney carcinoma library; they covered 27 kb and included full-length p53 gene of 19.5 kb and flanking sequences. From normal placenta libraries three overlapped clones were obtained. Restriction map of cloned sequences was constructed and polarity of the p53 gene determined. The first intron of the gene is large (10.4 kb); polymorphic BglII site was observed in this intron, which allows to discriminate between allelic genes. One of these (BglII-) is ten times more abundant that the other (BglII+). Both allelic genes are able to synthesize the 2.8 kb p53 gene.
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PMID:[Structural organization of the human p53 gene. I. Molecular cloning of the human p53 gene]. 282 91

Protein (m.v. 53 kilodalton) with electrophoretic mobility identical to that of protein detected in leukocytes of patients with Down's syndrome and of protein p53 obtained from mouse ascites carcinoma was demonstrated by polyacrylamide gel electrophoresis in healthy donors' leukocytes cultured with PHA and in peripheral blood of patients with chronic myeloleukemia. Appearance of the class p53 proteins in leukocytes of patients may be connected with the presence in their blood of the population of immature or transformed, proliferating or merely DNA-synthesizing leukocytes, particularly those amplifying the gene that codes protein p53.
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PMID:[Electrophoretic detection of protein p53 in human leukocytes]. 316 58

Immunohistochemical evaluation of 200 primary breast cancers with the anti-p53 mouse monoclonal antibody (MAb) PAb421 showed positivity in nuclei of malignant cells in 31 cases (15.5%). PAb421+ cases were significantly more frequently epidermal growth factor receptor (EGF-R)-positive (67.7%; p less than 0.001) and estrogen receptor (ER)-negative (73.3%; p less than 0.001); they displayed surface histocompatibility class-1 (80.6%; p less than 0.01) and 11 (74.2%; p less than 0.05) antigens. Low values for progesterone receptor (mean 67.20 +/- 25.2 fmol/mg; p less than 0.05) and a high number of cells positive for the proliferation-associated antigen Ki-67 (log mean 6.88 +/- 0.33; p less than 0.01) were found in PAb421+ tumors as well as a high number of grade-3 infiltrating duct carcinomas (70%; p = 0.01). Of the 200 cases of mammary carcinoma, 88 were further analyzed using another human specific anti-p53 MAb PAb1801, and 40 (45.5%) were found positive. This MAb stained all the PAb421+ cases and was significantly associated with negative ER status (39.5%; p less than 0.05) and high Ki-67 scores (log mean 6.93 +/- 0.24; p = 0.001). Analysis of PAb1801+/Pab421- cases for HLA antigens, EGF-R and ER showed a phenotype similar to that of the p53-ve/ER+ carcinomas, except for the high Ki-67 score. No differences in age of the patient, number of involved nodes, tumor size, ploidy or labelling index scores were evident between p53+ and carcinomas. We concluded that p53 in mammary carcinomas is associated with ER-negative, growth factor receptor-positive, high-grade tumors, and is a promising new parameter to evaluate the cellular biology and prognosis of breast cancer.
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PMID:P53 expression in breast cancer. 327 32

Transfection of a cloned p53 gene into a murine bladder carcinoma cell with a low metastatic capacity led to elevated levels of p53 protein in clonal transfectants. After intravenous inoculation into syngeneic mice, p53-transfected clones showed significantly increased metastatic potential in comparison with control transfectants. The observed change did not seem to be due to a change in growth potential per se since the cell lines showed similar growth properties in vitro.
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PMID:p53 increases experimental metastatic capacity of murine carcinoma cells. 329 Jun 47

The coordinate expression of the nuclear p53 protein, cytoplasmic intermediate filament vimentin (VIM) and membrane epidermal growth factor receptor (EGF-R) was significantly associated with oestrogen receptor immunocytochemical nuclear stain (ER-ICA) negative breast carcinomas. Twenty-three (51.1%), 26 (57.8%) and 27 (60%) of 45 ER-ICA -ve cancers were respectively p53 +ve, VIM +ve and EGF-R +ve; whereas of 151 ER-ICA +ve tumours 8 (5.3%) were p53 +ve (P less than 0.0001), 23 (15.2%) VIM +ve (P less than 0.001) and 40 (26.5%) EGF-R +ve P less than 0.001). Thirty-six of 45 (80%) ER-ICA -ve carcinomas were positive for at least one of the markers versus 55/151 (36.4%) ER-ICA +ve cases (chi 2 = 28.92, P less than 0.001). A prevalence of high grade carcinomas was found among p53 +ve, VIM +ve cases; the latter subset of tumours also had a larger mean diameter. These results suggest that ER -ve breast carcinoma cells display a coordinate expression of cell cycle-related proteins and marked changes of both the cytoskeleton and the membrane receptor repertoire.
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PMID:Vimentin and p53 expression on epidermal growth factor receptor-positive, oestrogen receptor-negative breast carcinomas. 329 21

To establish well-characterized cellular reagents for the study of colon carcinoma, we have examined 19 human colorectal carcinoma cell lines with regard to morphology, ultrastructure, expression of tumor-associated antigens, proliferative capacity in vitro, anchorage-independent growth, oncogene expression, tumorigenicity and malignant potential. Cell lines examined were cultured under identical conditions, and in vitro and in vivo analyses were performed in parallel on replicate cultures. Three classes of colorectal cell lines were defined according to their tumorigenicity in nude mice. Class-1 lines formed rapidly progressing tumors in nearly all mice at an inoculum of 10(6) cells. Cell lines belonging to class-2 were less tumorigenic, producing tumors later and at a slower growth rate. Class-3 lines were non-tumorigenic under all experimental conditions tested. By Northern analysis, the oncogenes c-myc, H-ras, K-ras, N-ras, myb, fos and p53 were expressed in nearly all cell lines examined. In contrast, transcripts for abl, src and ros were not detected. The best in vitro predictor of tumorigenicity was colony formation in soft agar. There was no detectable correlation between tumorigenicity and metastatic potential, doubling time in vitro, production of tumor-associated markers, xenograft histology or expression of specific oncogenes.
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PMID:Biological characterization and oncogene expression in human colorectal carcinoma cell lines. 333 74


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