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)

Sporadic colon carcinomas, carcinomas arising in chronic ulcerative colitis, and pancreatic adenocarcinomas have been analyzed for the presence of c-Ki-ras mutations by a combination of histological enrichment, cell sorting, polymerase chain reaction, and direct sequencing. Although 60% (37/61) of sporadic colon carcinomas contained mutations in codon 12, only 1 of 17 specimens of dysplasia or carcinoma from ulcerative colitis patients contained c-Ki-ras mutations, despite a high frequency of aneuploid tumors. In contrast, a higher percentage (16/20 = 80%) of pancreatic adenocarcinomas contained mutations in c-Ki-ras 2, despite a lower frequency of DNA aneuploidy in these neoplasms. Moreover, the spectrum of mutations differed between sporadic colon carcinoma, where the predominant mutation was a G to A transition, and pancreatic carcinomas, which predominantly contained G to C or T transversions. These results suggest that the etiology of ras mutations is different in these three human neoplasms.
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PMID:Frequency and spectrum of c-Ki-ras mutations in human sporadic colon carcinoma, carcinomas arising in ulcerative colitis, and pancreatic adenocarcinoma. 177 97

Malignant transformation of rodent cell lines by polyoma virus and by activated ras genes is associated with increased UDP-GlcNAc:Man alpha-R beta-1,6-N-acetylglucosaminyltransferase V (GlcNAc-transferase V) activity and it product -GlcNAc beta 1-6Man alpha 1-6Man beta 1-branched Asn-linked oligosaccharides. In this report, we have compared beta 1-6GlcNAc branching of core O- and N-linked oligosaccharides in three experimental models of malignancy, namely (a) rat2 fibroblasts and their malignant T24H-ras-transfected counterpart; (b) benign SP1 mammary carcinoma cells and two metastic sublines of SP1; and (c) the metastatic MDAY-D2 lymphoma cell line and its poorly metastatic glycosylation mutant KBL-1. In addition to the previously reported increase in GlcNAc-transferase V activity, UDP-GlcNAc:Gal beta 1-3GalNAc alpha-R (GlcNAc to GalNAc) beta-1,6-N-acetylglucosaminyltransferase (core 2 GlcNAc-transferase, EC 2.4.1.102) activity was found to be elevated by 70% in the malignant rat2 and SP1 cell lines while several other glycosyltransferase activities were not significantly different. The action of core 2 GlcNAc-transferase followed by beta 1-4Gal-transferase provides an N-acetyllactosamine antenna that can be extended with polylactosamine (i.e. repeating Gal beta 1-4GlcNAc beta 1-3) provided UDP-GlcNAc:Gal beta-R beta 1-3GlcNAc-transferase (GlcNAc-transferase) (i)) activity is present. Polylactosamine content in microsomal membrane glycoproteins was quantitated by labeling the GlcNAc termini resulting from the action of Escherichia freundii endo-beta-galactosidase with bovine galactosyltransferase/UDP-[3H] Gal. Glycopeptidase F- sensitive and -insensitive fractions were measured to assess the N- and O-linked components. In the SP1 tumor model, the metastatic sublines showed increased core 2 GlcNAc-transferase and GlcNAc-transferase V activities but no change in GlcNAc-transferase (i) activity, yet polylactosamine was increased in both O- and N-linked oligosaccharides. In rat2 cells, down-regulation of GlcNAc-transferase (i) following transformation was associated with decreased polyactosamine even though core 2 GlcNAc-transferase and GlcNAc-transferase V were elevated in the cells. Finally, a 3-fold decrease in GlcNAc-transferase V in KBL-1, the glycosylation mutant of MDAY-D2 cells, resulted in complete loss of polylactosamine in N-linked but no change in O-linked polylactosamine content. These results suggest that, provided GlcNAc-transferase (i) is not limiting, the beta 1-6-branching enzymes core 2 GlcNAc-transferase and GlcNAc-transferase V regulate the levels of polyactosamine in O- and N-linked oligosaccharides, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Increased UDP-GlcNAc:Gal beta 1-3GaLNAc-R (GlcNAc to GaLNAc) beta-1, 6-N-acetylglucosaminyltransferase activity in metastatic murine tumor cell lines. Control of polylactosamine synthesis. 182 44

The effects of three hormonal agents with a different mechanism of action (tamoxifen [TAM], medroxyprogesterone acetate [MPA] and estradiol [E2]) on tumor growth, differentiation and oncogene expression were evaluated using the estrogen-receptor positive human breast carcinoma cell line MCF-7 transplanted into nude mice. In MCF-7 tumors treated with E2, tumor incidence, mean weight of tumors, 3H-thymidine labelling index, differentiation antigen HMFGM (human milk-fat globule membrane) and ras p21, c-myc, neu oncogene products, the level was significantly increased. On the other hand MPA suppressed all of them. TAM increased the level of c-myc expression and HMFGM antigen, but suppressed the others. This evidence indicates that E2 induces both proliferation and differentiation of MCF-7 tumor cells. MPA suppresses both proliferation and differentiation, and TAM induces differentiation and suppresses proliferation.
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PMID:Effects of tamoxifen, medroxyprogesterone acetate and estradiol on tumor growth and oncogene expression in MCF-7 breast cancer cell line transplanted into nude mice. 183 73

The E7 protein is one of the principle transforming proteins encoded by human papillomavirus type 16 (HPV16), a virus strongly associated with the development of cervical carcinoma. In the present study we show that cotransfection of wild-type human or murine p53 sequences with E7 and ras markedly reduces transformation in baby rat kidney cells, although no effect of p53 is seen on the ability of E7 to transform an established mouse line to anchorage independence. In contrast, expression of mutant p53 strongly potentiates the transforming function of E7 and confers marked growth factor independence to cells cotransformed by E7 and ras. These data suggest that E7 and p53 function in separate yet complementary biochemical pathways.
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PMID:Modulation of immortalizing properties of human papillomavirus type 16 E7 by p53 expression. 184 4

Two human papillomavirus type 16 (HPV 16)-immortalized human keratinocyte cell lines (HPK) were shown to have retained the ability for differentiation after subcutaneous injection into nude mice. These properties were maintained even at late passage. HPK cells gave rise to transiently growing cysts which exhibited an epitheliumlike architecture. Moreover, differentiation-specific markers such as cytokeratin 10, involucrin, and filaggrin were shown to be expressed in an ordered succession. RNA-RNA in situ hybridization revealed heterogeneous and low levels of HPV 16 E6-E7 RNA in the basal layer of the cysts. In contrast, in progressively growing tumors induced by HPK cells containing an activated ras oncogene (EJ-ras) or in tumors induced by the cervical carcinoma cell line CaSki, high levels of E6-E7-specific RNA could be detected. Irrespective of the growth potential of these cell lines in nude mice, viral transcription was always more evident in the basal layer and in proliferatively active cells rather than in differentiated cells. This contrasts with viral gene expression in HPV 16 positive low-grade cervical dysplasia, in which abundant viral transcriptional activity was mapped to the upper third of the epithelium. It is suggested that the physical state of the viral DNA, i.e., integrated viral DNA in the cell lines as opposed to extrachromosomal DNA in low-grade cervical dysplasia, may influence viral gene regulation.
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PMID:Inverse relationship between human papillomavirus (HPV) type 16 early gene expression and cell differentiation in nude mouse epithelial cysts and tumors induced by HPV-positive human cell lines. 184

Human papillomavirus type 6 (HPV-6) is predominantly associated with benign genital warts whereas HPV-16 and HPV-18 are detected predominantly in carcinomas of the lower genital tract; HPV-6 is found rarely in such carcinomas. Experiments were designed to discriminate between two hypotheses concerning the role of HPV-6 in the genesis of a genital tract carcinoma: (i) the HPV-6 in the carcinoma (HPV6-T70) differs genetically from HPV-6 in a benign lesion (HPV6-W50), giving HPV6-T70 properties similar to those of HPV-16/18: (ii) HPV6-T70 and HPV6-W50 have similar biological activity, suggesting that the role of HPV-6 in oncogenesis is different from that of HPV-16/18. Restriction enzyme digestion and DNA sequence determination established that HPV6-T70 differs from HPV6-W50 in the upstream regulatory region (URR) but not in the proteins encoded by open reading frames (ORFs) E5, E6 or E7, ORFs implicated in oncogenesis. To determine whether the difference in the URR sequence could alter the level of expression of viral genes, the URRs were cloned into the enhancerless plasmid pSVEcat. Analysis of chloramphenicol acetyltransferase activity after transfection into HeLa and Vero cells showed that the URRs had comparable enhancer activity. Cotransfection of baby rat kidney (BRK) cells with HPV6-T70 and an activated ras gene indicated that, in contrast to HPV-16 and HPV-18, this HPV-6 genome could not cooperate with ras to transform BRK cells. The data suggest that HPV6-T70 and HPV6-W50 have similar enhancer activity and transforming potential.
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PMID:Relative enhancer activity and transforming potential of authentic human papillomavirus type 6 genomes from benign and malignant lesions. 184 89

The possible point-mutational activation of the ras oncogene, which probably contributes to the evolution of aldosterone-producing adenomas and ectopic reninoma, was evaluated. Chromosomal DNA was extracted from six aldosterone-producing adenomas and one renin-secreting liver carcinoma, using the standard method with phenol:chloroform:isoamyl alcohol. One microgram of sample DNA, forward and reverse primers, Taq I polymerase and deoxyribonucleotide triphosphates (dNTPs) were mixed and the ras gene was amplified by the polymerase chain reaction. Point mutations at ras-12 or ras-61 sites of amplified DNA were tested by dot-blotting, using H-, N- and K-ras oligonucleotide probes with mutations at codons 12 or 61. However, there were no point mutations at amino acid codons 12 or 61 of c-Hi-ras, c-Ki-ras and N-ras oncogenes in all aldosterone-producing adenomas and the one ectopic reninoma. These results indicate that point-mutational activation of ras oncogenes does not contribute, at least in this series, towards the evolution of aldosterone-producing adenomas and the reninoma.
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PMID:Contribution of the activation of the ras oncogene to the evolution of aldosterone- and renin-secreting tumors. 184 28

We have used derivatized antisense oligodeoxynucleotides both in vitro and in vivo specifically to inhibit translation of the activated human oncogene Ha-ras. The oligonucleotides (5'-CCACACCGA-3') were targeted to a region of Ha-ras mRNA including the point mutation G----T at the 12th codon which leads to a Gly----Val substitution in the ras p21 protein. They were linked to an intercalating agent and/or to a hydrophobic tail, both to increase their affinity for their mRNA target and to enhance their uptake by tumor cells. A cell-free translation system was used to demonstrate an RNase H-dependent specific inhibition of activated ras protein synthesis. 50% inhibition was observed at a concentration of 0.5 microM of the most efficient oligonucleotide (5'-substitution with an acridine derivative and 3'-substitution by a dodecanol chain). This inhibitory effect stems from a point mutation-sensitive cleavage of the mRNA and it mirrors the growth inhibition obtained with T24 bladder carcinoma cells, which carry activated Ha-ras. The proliferation of HBL100 cells (non tumorigenic human mammary cell line) which carry two copies of normal Ha-ras was unaffected. This study shows that it is possible to design antisense agents that will inactivate the mutated oncogene but not the protooncogene which is generally essential to cell survival.
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PMID:Short modified antisense oligonucleotides directed against Ha-ras point mutation induce selective cleavage of the mRNA and inhibit T24 cells proliferation. 185 Jun 94

A papillomatous cyst was induced by implanting bovine foetal palate epithelium, infected in vitro with bovine papillomavirus type 4 (BPV-4), beneath the renal capsule of a nude mouse. The benign tumour underwent malignant progression, developing into a squamous cell carcinoma with metastatic deposits in the spleen. The bovine origin of both the renal and splenic cancers was confirmed by the presence of bovine major histocompatibility complex class I antigens in the cancer cells and by sequencing the Harvey-ras 1 gene, which was shown to be of bovine origin. BPV-4 DNA was present in the residual papillomatous fronds of the renal cancer, but was absent from the carcinoma proper and for the splenic metastasis. These results confirm that BPV-4 is a carcinogenic agent and that its genetic information is not necessary for the maintenance of the malignant phenotype. Moreover the system provides the opportunity to investigate the role of viral and chemical carcinogens in an experimental system.
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PMID:Malignant transformation of a papilloma induced by bovine papillomavirus type 4 in the nude mouse renal capsule. 185 17

We have established a reliable method to induce invasive and non-invasive carcinomas in the heterotopically transplanted urinary bladder of rats by repeated injection of N-methyl-N-nitrosourea (MNU), and examined the alterations of the ras oncogenes and ras oncogene product (p21) in the induced tumours. The incidence of muscle-invasive carcinomas was proportional to the total dose of MNU. When 5, 6 or 12 doses of MNU were used, muscle invasive carcinomas developed in 22, 58 or 45% of animals, respectively, after a mean observation period, respectively, of 54 +/- 9, 45 +/- 13 and 38 +/- 3 weeks. Whereas activated H-ras gene was detected in only one non-invasive carcinoma by DNA transfection assay, seven of 18 non-invasive and invasive carcinomas showed activated ras p21 when examined by immunoblot analysis. Amplification or rearrangement of myc or epidermal growth factor (EGF) receptor gene was not observed. The results indicate that alterations of ras gene may be involved in the development of rat bladder carcinomas but not of invasiveness.
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PMID:ras gene alterations in invasive and non-invasive rat bladder carcinomas induced by N-methyl-N-nitrosourea. 185 7


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