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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bladder tumors were induced in male F344/NCr rats by administration of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at 500 p.p.m. in their drinking water for 12 weeks. Twenty-one bladder tumors that developed between 25 and 50 weeks after BBN administration was begun were evaluated for immunoreactivity with polyclonal or monoclonal antibodies raised against ras p21, for amplification of ras genes by Southern blotting, and for activating point mutations in ras genes by selective oligonucleotide hybridization of products from polymerase chain reaction (PCR). Increased expression of ras p21 was detected by avidin-biotin immunohistochemistry in 18/21 (85%) of the neoplastic bladder lesions. By Southern analysis, there was no significant amplification of H-ras, K-ras or N-ras in any of the tumors except one that showed a 5-fold amplification of K-ras. Point mutations in ras genes were detected by selective oligonucleotide hybridization of the products of PCR. Of the 21 bladder tumors, three tumors were shown to have mutations in codon 12 (GGA----GAA), six tumors in codon 61 (two CAA----CTA, four CAA----CGA), and one in both codon 12 (GGA----GAA) and codon 61 (CAA----CGA), all in H-ras. Thus 10 of 21 tumors has ras gene mutations in a portion of the tumor cells. The variable pattern of point mutation in H-ras suggests that these mutations may not all be a direct consequence of interaction of BBN metabolites with H-ras. Enhanced expression of ras p21 was always focal and was not necessarily associated with transforming ras mutations. It is therefore suggested that tumorigenesis in BBN-initiated bladder cells might involve H-ras activation as part of a multistep pathway; however, H-ras involvement is not obligatory for tumor development.
Carcinogenesis 1990 Dec
PMID:H-ras activation and ras p21 expression in bladder tumors induced in F344/NCr rats by N-butyl-N-(4-hydroxybutyl)nitrosamine. 226 74

We have recently found that ras oncogene product (p21) inhibits cysteine proteinases. Because p21 transforms NIH3T3 cells and also induces differentiation of PC12 pheochromocytoma cells, several potent cysteine proteinase inhibitors have been tested for whether they show similar biological activities. The saturation density of NIH3T3 cells was increased by repeated treatment with cysteine proteinase-specific inhibitors such as N-acetyl-leucyl-leucyl-norleucinal (ALLN), N-acetyl-leucyl-leucyl-methioninal (ALLM), E-64 and chicken egg white cystatin. Furthermore, some transformed foci appeared a few weeks after the onset of the treatment. ALLN and ALLM were also able to induce neurite outgrowth of PC12 cells. Taken together, the cysteine proteinase-specific inhibitory activity of p21 may be important for its biological activities.
Carcinogenesis 1990 Jan
PMID:Cysteine proteinase inhibitors and ras gene products share the same biological activities including transforming activity toward NIH3T3 mouse fibroblasts and the differentiation-inducing activity toward PC12 rat pheochromocytoma cells. 240 61

We recently developed rat fibroblast cell lines that stably overproduce high levels of the beta 1 form of protein kinase C (PKC). These cells display several disorders in growth control and form small microscopic colonies in agar. In the present study we demonstrate that one of these cell lines, R6-PKC3, is extremely susceptible to transformation by an activated human bladder cancer c-H-ras oncogene (T24). Compared with control cell line R6-C1, T24-transfected R6-PKC3 cells yielded a 10-fold increase in the formation of large colonies in agar. Cell lines established from these colonies displayed a highly transformed morphology, expressed the T24-encoded p21 ras protein, continued to express high levels of PKC, and were highly tumorigenic in nude mice. These results provide genetic evidence that PKC mediates some of the effects of the c-H-ras oncogene on cell transformation. Data are also presented suggesting that optimum synergistic effects between c-H-ras and PKC require critical levels of their respective activities. These findings may be relevant to the process of multistage carcinogenesis in tissues containing cells with an activated c-H-ras oncogene.
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PMID:Cells that overproduce protein kinase C are more susceptible to transformation by an activated H-ras oncogene. 247 57

The injection of a retrovirus carrying the v-ras-Ki oncogene into the thyroid gland of adult Fischer rats induces thyroid carcinomas when associated with a treatment of the animals with a goitrogenic agent. More than one hundred adult Fischer rats have been treated with the goitrogen agent propylthiouracil in order to induce thyroid hyperplasia. Twenty days after treatment, rat thyroid glands, surgically prepared, were injected with the Kirsten murine sarcoma virus (KiMSV). Within three months more than 90% of the animals developed thyroid tumors. Histologically the tumors had the appearance of well differentiated carcinomas. Thirty animals had lung metastases in addition to the thyroid carcinoma. The presence of KiMSV specific transcripts and the specific transforming protein (p21) in thyroid carcinomas and in the metastases was detected by Northern blot analysis and immunoprecipitation, respectively. Only three rats, among thirty that had not received the goitrogen treatment, but only the injection with KiMSV, developed thyroid carcinomas of very small size and with a very long latency period (almost one year). The results described represent the first instance of thyroid carcinoma induction by retroviruses. This system may be regarded as a useful model to investigate the process of thyroid carcinogenesis in vivo. These results suggest that this model may also be useful for investigating the interaction between hormones and cells harboring the activated oncogene in the development of thyroid carcinoma since activated ras oncogenes have been implicated in human thyroid carcinoma.
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PMID:The Kirsten murine sarcoma virus induces rat thyroid carcinomas in vivo. 253 91

The expression of the ras gene product p21 in normal gastric mucosa, early gastric carcinoma of diffuse (gastric) and intestinal types, and in adjacent mucosal abnormalities is reported. The analysis was performed on paraffin sections by an immunohistochemical assay using the mouse monoclonal antibody RAP-5 and the rat monoclonal antibody Y13-259. Expression of ras p21 was assessed by staining intensity and percentage of positively stained cells. In comparison to normal gastric mucosa of non-cancer patients, p21 was overexpressed in nearly all early carcinomas of both types and in the dysplastic and/or metaplastic mucosal alterations accompanying intestinal type of gastric cancer. Increased p21 expression was also observed in the normal-appearing mucosa adjacent to early carcinomas of diffuse type, but not in the morphologically normal gastric epithelium adjacent to the intestinal type. The results of this investigation suggest that ras p21 overexpression may be related to early events of human gastric carcinogenesis. The study supports the notion of different pathways in the development of diffuse (gastric) and intestinal types of gastric carcinomas.
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PMID:Expression of ras oncogene p21 protein in early gastric carcinoma and adjacent gastric epithelia. 255 Jan 23

Aberrant proto-oncogene expression has been implicated in hepatic cell proliferation, transformation and carcinogenesis using a rat model. To investigate the role of ras p21 product expression in human hepatocellular carcinoma (HCC), we have localized ras p21 in formalin fixed, paraffin-embedded normal and abnormal livers utilizing the avidin-biotin peroxidase method and a monoclonal antibody to ras-gene product p21. A semi-quantitative estimate of p21 expression was performed by serial dilutions of primary antibody. While low dilutions of anti-p21 stained normal hepatocytes, higher dilutions failed to react with normal hepatocytes and these dilutions were used for assessment of p21 enhancement. Increased p21 expression of ras oncogene in HCC occurs in fibrolamellar carcinomas and other better differentiated HCC. Tumor dedifferentiation is associated with an attenuation of p21 expression. Liver adjacent to HCC exhibits p21 enhancement, in contrast to liver surrounding metastatic carcinoma, suggesting increased p21 expression in HCC induction.
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PMID:ras oncogene p21 expression in hepatocellular carcinoma. 255 Jun

The cell line TE671 has been widely used as a model of human medulloblastoma. In the present study we have demonstrated that transfection of DNA from this cell line into NIH 3T3 cells reveals the presence of an activated N-ras gene. Using oligonucleotide probes we have shown that the N-ras gene is activated by a point mutation at the third base of codon 61 resulting in the substitution of histidine for glutamine in the p21 ras gene product. We noted that this relatively uncommon activating mutation is also present in the human rhabdomyosarcoma cell line RD. Based on this finding and on the observation that several of the phenotypic characteristics of TE671, such as the presence of muscle-type nicotinic acetylcholine receptors and the intermediate filament protein desmin, are suggestive of myoid origin we investigated the possible identity of these two cell lines. Cytogenetic analysis revealed the presence of marker chromosomes common to both TE671 and RD. DNA fingerprinting using both locus specific and multilocus core probes showed indistinguishable band patterns in the two cell lines. Taken together our data show that TE671 and RD are derivatives of the same cell line and we conclude that the properties of the TE671 line should be ascribed to rhabdomyosarcoma rather than medulloblastoma cells.
Carcinogenesis 1989 May
PMID:Characterization of the human cell line TE671. 265 Sep 8

The modulation of gap junctional intercellular communication (GJIC) plays an important role during tumor promotion. Several tumor-promoting agents are known to inhibit this form of cellular coupling. In addition, tumor cells and cells expressing certain oncogenic products have been shown to exhibit inhibited or reduced GJIC. The Ha-ras oncogene is expressed in a wide variety of human tumors from different tissues. Its p21 product is a membrane-bound polypeptide, the function of which is not fully characterized. We tested the effects of the expression of the human c-Ha-ras-1 oncogene, derived from the EJ/T4 bladder carcinoma cell line, on the ability of the Chinese hamster V79 cells to conduct gap junctional communication. The junctional competence was studied by two different methods, the scrape-loading/dye transfer technique and the metabolic cooperation assay. The results indicate a strong correlation between the expression of p21 ras protein and the inhibition of gap junctional function. Assuming that reversible inhibition of intercellular communication plays a role during tumor promotion and stable inhibition during the tumor progression phase of carcinogenesis, our data suggest that, while chemical tumor promoters and the ras oncogenes might work by different biochemical mechanisms, they both affect a critical cellular function; namely, GJIC.
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PMID:Potential role of the human Ha-ras oncogene in the inhibition of gap junctional intercellular communication. 267 3

In the present study, monoclonal antibody rp-28 directed against the ras gene product p21 was used to evaluate ras p21 expression in malignant and benign ovarian tissues. Some ovarian carcinomas (serous cystadenocarcinoma, mucinous cystadenocarcinoma, undifferentiated carcinoma and clear cell carcinoma) demonstrated intense staining of ras p21. In mucinous tumors, both the frequency of ras p21 positive staining and the staining intensity gradually increased with the degree of malignancy. There was no difference in ras p21 expression according to the clinical stages of ovarian carcinomas. In the metastatic lesions, ras p21 staining was rather weaker than in the primary lesions. It is therefore possible that intense staining of ras p21 is associated with the degree of malignancy in some types of ovarian tumors, and that the expression of ras oncogene product p21 is not enhanced with progression and metastasis in such types of ovarian carcinoma. These results suggest that ras oncogene plays an important role in the carcinogenesis of some types of epithelial ovarian tumors.
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PMID:[Immunohistochemical studies of ras oncogene product p21 in human ovarian tumors]. 268 41

Mouse skin papillomas and squamous cell carcinomas induced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with phorbol esters, such as 12-O-tetradecanoyl phorbol-13-acetate, frequently contain an activated Harvey ras gene. Six murine epidermal cells lines established from pooled skin papillomas previously tested negative in the NIH-3T3 assay, but have an altered differentiation program by a variety of criteria. The Harvey ras gene and its p21 protein product from these cell lines have been analyzed for alterations responsible for their altered growth and differentiation properties that were undetectable by 3T3 transfection assays. In comparison with primary papillomas and carcinomas, shown to have a point mutation in codon 61 of the Harvey ras gene, resulting in a p21 product with the diagnostic alteration in SDS-PAGE, the papilloma cell lines exhibited neither the codon 61 mutation, nor p21 product with altered migration in SDS-PAGE. These findings suggest that these papilloma cell lines contain a genetic lesion(s), other than Harvey ras activation, that may be responsible for their altered epithelial differentiation patterns and thus may serve as a useful model for identifying lesions involved in malignant conversion.
Carcinogenesis 1987 Dec
PMID:Analysis of the rasH oncogene and its p21 product in chemically induced skin tumors and tumor-derived cell lines. 282 83


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