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)

One hundred and nine samples comprising carcinomas, adenomas, dysplastic, inflamed and normal mucosa from patients with sporadic colon cancer and ulcerative colitis (UC) were analysed for c-Ki-ras mutations. DNA was extracted from archival paraffin-embedded material, amplified using the polymerase chain reaction (PCR) and the PCR products analysed using restriction enzyme digestion. Forty-two per cent (14/33) of the sporadic carcinoma controls contained Ki-ras codon 12 mutations in contrast to 24% (8/33) of ulcerative colitis carcinomas. A significantly higher c-Ki-ras mutation rate was observed in rectal carcinomas (72%) in comparison to colonic carcinomas (28%) in control patients (P less than 0.04), while the opposite was observed in UC patients. The difference between the incidence of c-Ki-ras mutations in rectal carcinomas in UC (9%) and in sporadic rectal carcinomas (72%) was also significant (P less than 0.01). This lower prevalence rate and different site distribution of c-Ki-ras mutations in UC carcinomas compared to sporadic carcinomas suggests that specific genetic differences may underlie the causation of carcinomas arising in these situations.
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PMID:c-Ki-ras gene mutations in dysplasia and carcinomas complicating ulcerative colitis. 185 18

The p53 tumor suppressor gene is frequently mutated and the K-ras oncogene is occasionally mutated in primary specimens of human lung carcinomas. These mutated genes also cooperate in the immortalization and neoplastic transformation of rodent cells. To determine whether these mutations are necessary for maintenance of the immortalized and/or neoplastically transformed states of human bronchial epithelial cells, the p53 gene and regions of the ras (K-, H-, and N-) genes were sequenced in nine human lung carcinoma cell lines. Detection of p53 mutations by polymerase chain amplification and direct DNA sequencing was corroborated by p53 immunocytochemistry and coimmunoprecipitation of p53 with heat shock protein 70. p53 and ras genes were frequently, but not always, mutated in the carcinoma cell lines. These data are consistent with the hypothesis that multiple genetic changes involving both protooncogenes and tumor suppressor genes occur during lung carcinogenesis.
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PMID:p53 mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines. 185 24

Six families of activated protooncogenes, ras, raf, fur, neu, jun and myc have so far been associated with human lung cancer. Human bronchial epithelial cells in vitro are being used to investigate the functional role of these specific oncogenes and growth regulatory genes in carcinogenesis and tumour progression. When transferred into normal human bronchial epithelial cells by the highly efficient protoplast fusion method, the v-Ha-ras oncogene initiates a cascade of events leading to decreased responsiveness of these cells to inducers of squamous differentiation, aneuploidy and, less frequently, 'immortality' and tumorigenicity with metastasis in athymic nude mice. Transfection of the SV40 T antigen gene results in nontumorigenic cell lines that have a nearly normal pathway of terminal squamous differentiation and can be transformed into malignant cells by transfected Ha-ras, N-ras or Ki-ras. The combination of transfected c-myc and c-raf-1 also transforms human bronchial epithelial cells into neoplastic cells that exhibit some phenotypic traits found in small-cell carcinomas. These and other results indicate that proto-oncogenes dysregulate the pathways of growth and differentiation of human bronchial epithelial cells and play an important role in human carcinogenesis. Analyses of allelic deletion and somatic cell hybrids are being used to identify the chromosomal localization of tumour suppressor genes. We have examined 54 non-small-cell bronchogenic carcinomas with 13 polymorphic markers. Loss of heterozygosity was more frequent than among 23 squamous-cell carcinomas than among 23 adenocarcinomas or eight large-cell carcinomas. Loss of heterozygosity for chromosome 17p was found in 89% of cases of squamous-cell carcinoma and 18% of adenocarcinomas. Analysis of chromosome 11 for allelic deletions revealed two commonly deleted regions (11p13 and 11p15.5). Somatic cell hybrids between normal human bronchial epithelial cells and Hut292DM, a lung carcinoma cell line, had a finite lifespan in vitro and were nontumorigenic in athymic nude mice. Tumour suppressive effects of individual or combinations of specific human chromosomes on Hut292DM are being examined by formation of microcell-cell hybrids. Chromosome 11 has tumour suppressor activity in these hybrids. Both of these studies suggest that tumour suppressor genes play a dominant role in lung carcinogenesis and provide in-vitro model systems for isolating these genes by subtraction library and insertional mutagenesis techniques.
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PMID:Role of oncogenes and tumour suppressor genes in human lung carcinogenesis. 185 68

The non tumorigenic human mammary cell line HBL100 has been transformed by the EJ/T24 human bladder carcinoma Harvey(Ha)-ras oncogene. Six cell lines were established from transformed colonies. They all expressed a high level of the ras oncogene and were tumorigenic in athymic nude mice. During an in vivo passage in animals, tumour cells presenting a growth advantage were selected, and some of the tumours revealed an amplification of the transfected ras sequences. Using this model of human cell transformation, we have isolated a cDNA clone corresponding to a heat shock protein gene (hsp89 alpha). This gene, normally transcribed at a higher rate in response to serum stimulation, was found to be constitutively overexpressed in ras-transformed HBL100 cells. In contrast, a closely related hsp gene (hsp89 beta), remained sensitive to serum stimulation, in both untransformed and ras-transformed HBL100 cells. Thus, the regulation of the expression of the hsp89 genes, upon serum stimulation, involves ras-dependent and ras-independent pathways. Constitutive overexpression of the murine homolog of the hsp89 alpha was observed in NIH3T3 cells transformed by the three ras oncogenes, but not with some other oncogenes. Therefore, alteration of the hsp89 alpha gene expression is not a general characteristic of transformed cells, but seems to be linked to ras transformation.
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PMID:Constitutive overexpression of a 89 kDa heat shock protein gene in the HBL100 human mammary cell line converted to a tumorigenic phenotype by the EJ/T24 Harvey-ras oncogene. 186 62

Recent studies have shown that orthotopic (transurethral) transplantation of human bladder cancer cell lines into nude mice permits tumor growth that more accurately reflects their clinical malignant status in the original host. We have previously demonstrated that transfection and overexpression of normal or mutated c-Ha-ras genes into a noninvasive human papillary transitional cell carcinoma cell line confer upon these cells an invasive phenotype in vivo with behavior remarkably similar to the clinical behavior of high grade bladder carcinomas. Since elevated expression levels of the epidermal growth factor receptor (EGF-R), in addition to that of c-Ha-ras, have been correlated with transitional cell carcinoma progression, we sought to determine whether up-regulation of the EGF-R had occurred in the invasive high ras expressors and if so, what functional significance this might have. Our results show that invasive cell lines which overexpress the c-Ha-ras gene also have increased epidermal EGF-R expression. This was found to occur at both the protein and mRNA levels, and analysis of the EGF-R promoter/enhancer sequences has revealed a putative AP-1 site which may possibly enhancer sequences has revealed a putative AP-1 site which may possibly serve as a ras response element. In addition, we found that the cells overexpressing the EGF-R had acquired a positive sensitivity to the stimulatory mitogenic effects of EGF. Hence, the results obtained suggest a role for either a normal or a mutated overexpressing Ha-ras in up-regulating the surface EGF-R, possibly through an AP-1 site during human bladder carcinoma progression; they also highlight the potential that EGF may have in cooperating with this EGF-R up-regulation to help mediate enhanced tumor growth.
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PMID:Ha-ras induction of the invasive phenotype results in up-regulation of epidermal growth factor receptors and altered responsiveness to epidermal growth factor in human papillary transitional cell carcinoma cells. 186 71

Regarding to the pancreatic cancer, outcomes of the patients surgically treated have been poor. By using polymerase chain reaction (PCR), paraffin-embedded specimens of the pancreatic carcinoma were confined point mutation in Kirsten (K)-ras codon 12. Then, incidence and type of point mutation of this oncogene and correlative studies with stage, T or N factor of pancreatic cancer were analysed. Extremely high incidence of K-ras gene mutation was shown in present report. The highest mode of point mutation of K-ras oncogene was GGT to GAT coded aspartic acid. Cases without point mutation in K-ras codon 12 were significantly frequent in papillary adenocarcinoma than in tubular type. There were not correlative result among mutation types, stage and T factor of pancreatic cancer. Most patients with pancreatic cancer who survived more than 2 years have not shown mutation to aspartic acid. Four cases including two cases of mucin producing pancreatic cancer did not have point mutation in K-ras codon 12. Pathogenesis of mucin producing cancer can be distinguished from typical pancreatic cancer by detection of point mutation in K-ras codon 12 using PCR.
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PMID:[Detection of point mutation of Kirsten ras oncogene in pancreatic carcinoma by polymerase chain reaction]. 187 May 74

The relationship between the expression of a mutant ras gene in epithelial cells and loss of responsiveness to the negative effects of transforming growth factor beta (TGF-beta) is presently unclear. We have investigated this question using a series of cell lines derived from benign and malignant mouse skin tumours which express mutant forms of the H-ras gene. Immortalised, non-tumorigenic mouse epidermal cells respond to TGF-beta by cessation of growth, whereas in a series of malignant carcinoma lines the response was substantially reduced. Introduction of a mutant H-ras gene into the immortalised cells did not lead to any appreciable change in TGF-beta responsiveness, suggesting that initiation of carcinogenesis by ras mutation does not directly alter growth control by this pathway. Of two non-tumorigenic papilloma lines tested which had mutant H-ras genes, one retained complete sensitivity to TGF-beta, whereas the other showed a similar response to carcinomas. We conclude that growth control by TGF-beta is lost at a relatively late stage of carcinogenesis in this system, and is independent of ras gene activation.
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PMID:Loss of growth control by TGF-beta occurs at a late stage of mouse skin carcinogenesis and is independent of ras gene activation. 188 17

The presence of point mutation at codons 12, 13 and 61 of the c-Ki-ras oncogene was investigated in 7 cases of gastric adenoma and 35 cases of gastric adenocarcinoma using DNA samples from formalin-fixed and paraffin-embedded tissues. Oligonucleotides encompassing the three codons were amplified by using the polymerase chain reaction (PCR), and then examined for point mutation by the selective oligonucleotide hybridization technique. Point mutation was detected in three of the 7 adenomas (43%) and three of the 35 carcinomas (9%). All the gastric adenomas showed the histology of tubular adenoma, being very similar to that of colonic adenoma. The 35 cases of gastric adenocarcinoma were classified into 17 cases of differentiated type and 18 cases of undifferentiated type including signet-ring cell carcinoma. The point mutation of c-Ki-ras oncogene was detected only in the differentiated type (3/17, 18%), and there was no case with point mutation in the undifferentiated type. These results suggest that the genetic mechanism of carcinogenesis differs between the differentiated type and the undifferentiated type of gastric adenocarcinoma, and also that c-Ki-ras activation is possibly involved in a relatively early step of the "adenoma-carcinoma sequence," which leads to the development of a portion of differentiated adenocarcinomas in the stomach.
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PMID:Point mutation of c-Ki-ras oncogene in gastric adenoma and adenocarcinoma with tubular differentiation. 190 52

To determine if activation of the c-Ha-ras-1 gene is involved in the acquisition of growth factor independence in 7,12-dimethylbenz[a]anthracene (DMBA)--and N-nitrosomethylurea (NMU)--induced rat mammary carcinomas, three strategies were used. First, Ha-ras DNA from growth factor-independent DMBA-induced rat mammary tumor cells was amplified using the polymerase chain reaction and examined for the presence of mutations in the first and second exons of Ha-ras-1 by restriction fragment length polymorphism analysis, allele-specific oligonucleotide hybridization, and direct sequencing. No mutations were found in the codon 12/13 or codon 61 regions of the Ha-ras-1 gene. Second, a similar analysis of an NMU-induced mammary carcinoma showed that it harbored an activating mutation in codon 12 of Ha-ras-1. When analyzed for growth factor requirements, these cells were found to express limited growth potential in all media tested, in contrast to growth factor-independent cells, which proliferated extensively in the presence or absence of exogenous growth factors. Third, growth factor-dependent rat mammary tumor cells and spontaneously immortalized rat normal mammary epithelial cells were transfected with an activated form of the Ha-ras-1 (T24) gene, and the growth factor requirements of the transfected cells were examined. The ras-transfected cells retained the growth factor requirements of the normal cells. In addition, ras-transfected cells were transplanted into syngeneic rats and nude mice, and no tumors developed after 6 mo in vivo. These results indicate that, in rat mammary tumor cells, neither growth factor independence in vitro nor transplantability are directly mediated by Ha-ras oncogenes. The results also suggest that ras activation and growth factor independence may be associated with independent pathways to malignancy in rat mammary tumorigenesis.
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PMID:The role of Ha-ras oncogenes in growth factor independence in rat mammary carcinoma cells. 190 45

Susceptibility to mammary cancer in rats is genetically controlled by both susceptibility and suppressor genes. The Copenhagen (COP) rat strain is highly resistant to both spontaneous and induced mammary carcinogenesis. The resistant trait is due to the inheritance of an autosomal dominant allele termed mammary carcinoma suppressor (mcs) gene. To test whether the activity of mcs gene can suppress the transforming potential of an activated oncogene, we introduced v-H-ras oncogene into COP mammary epithelial cells in situ using a replication-defective retroviral vector. v-H-ras transfer caused the rapid development of mammary carcinomas at high multiplicities. Hormonal promotion further increased the penetrance of the activated ras gene. Compared with the mammary carcinoma-susceptible Wistar Furth (WF) rat strain, tumor development in the COP rat followed analogous kinetics. However, COP tumors were more differentiated and less locally invasive than were WF tumors. The possible role of the mcs gene in mammary differentiation is discussed.
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PMID:Overcoming the activity of mammary carcinoma suppressor gene in Copenhagen rats by v-H-ras oncogene transfer into mammary epithelial cells in situ. 191 52


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