Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oncogenes most frequently detected in human tumors belong to the ras gene family (Ha-ras, Ki-ras, and N-ras). These genes encode a group of closely related 21,000 dalton proteins termed p21. An immunohistochemical study of ras p21 expression was carried out on paraffin sections of 54 human breast carcinomas using monoclonal antibodies to p21. The control group consisted of ten cases of benign fibrocystic disease. The p21 expression was significantly higher in cancer cells than in epithelial cells of control specimens. No correlations, however, were observed between oncogene product expression and tumor size, histologic type, or grade. As a group, tumors with axillary lymph node metastases expressed higher levels of ras p21 than nonmetastasizing tumors. However, because of the significant overlap in individual p21 values, it is unlikely that the immunohistochemical assay for p21 could be used to predict the behavior of mammary carcinomas.
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PMID:Expression of ras oncogene p21 protein in relation to regional spread of human breast carcinomas. 246 32

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

A patient with two intracerebral glioblastomas of differing histology with metastases to the liver in the absence of surgery is reported. The gliomatous nature of the lesions was confirmed by staining for glial fibrillary acidic protein. Histological and immunohistochemical evidence suggests that the metastases arose from the more poorly differentiated of the intracerebral tumors. One of the intracerebral tumors had enhanced expression of the ras p21 oncogene as compared to the other tumors and as compared to nonmalignant brain tissue from this patient.
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PMID:Multifocal glioblastoma with liver metastases in the absence of surgery. Case report. 255 82

Three chromosome regions, i.e., 11p15, 13q, and 17p, were previously reported by three independent groups to be specifically reduced to hemizygosity in human primary breast cancer. We examined the DNA of 64 mammary tumors for loss of heterozygosity (LOH) with 28 polymorphic DNA markers dispersed on 10 arms of 8 different chromosomes. Complete or near-complete absence of LOH was observed on 5 arms (5 chromosomes). LOH at all three previously invoked regions was confirmed, and the highest frequency was found on 17p (67% of heterozygous patients). Allele loss of a marker from chromosome 3 (region p14-p21) was found in 7 of 15 informative cases. Concurrent LOH at 2 to 4 loci was noted in 20 of the 43 tumors showing LOH. Allele losses did not correlate with any of the six clinico-histopathological variables investigated, but in a group of patients in which we were unable to demonstrate LOH, the absence of distant metastases was statistically significant (P less than 0.05). These results suggest that some of the observed allele losses reflect random events, possibly as a result of genetic instability, but are not without biological significance for the progression of particular subclasses of breast tumors.
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PMID:At least four different chromosomal regions are involved in loss of heterozygosity in human breast carcinoma. 257 86

To gain a better understanding of the biologic development of rectal adenocarcinomas, the authors evaluated the level of ras gene protein product (p21) in the available material of 74 Dukes' B adenocarcinomas, 64 Dukes' C adenocarcinomas, and 60 lymph-node metastases resected at the University of Chicago Medical Center between 1965 and 1981. Pathologic slides and archival paraffin blocks were retrieved for confirmation of the original diagnosis and measurement of p21 content. P21 titers were obtained using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution giving definitive staining using the avidin-biotin peroxidase method. The analysis indicated that a higher percentage of Dukes' stage C rectal adenocarcinomas had high (greater than or equal to 1:40,000) p21 titers than Dukes' B adenocarcinomas (68.8 vs. 51.4 percent, respectively, P less than 0.05). In view of recent data suggesting that ras oncogene expression confers invasive and metastatic capabilities to NIH 3T3 cells, the authors believe this study offers evidence that overexpression of ras oncogene with overproduction of p21 protein product may be an important prerequisite for the acquisition of metastatic capabilities in the early stages of colon cancer.
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PMID:Ras oncogene and the acquisition of metastasizing properties by rectal adenocarcinoma. 266 52

It is now established that ras oncogenes can induce metastatic characteristics in primary diploid fibroblasts, nonsenescing fibroblasts and nonmetastasizing tumors. The issue of whether ras is directly involved in maintaining the metastatic phenotype through the expression and action of its gene product has been examined by analyzing the relationship to ras expression and to the production of the p21 ras-GTP complex, which is thought to mediate ras-transforming activity. While these expression and mutation studies support the idea that p21 ras directly regulates metastasis formation, it is also evident that there are many examples of human and murine cancers which show no differences in ras expression in primary and metastatic tumor cells. This may be partially explained by the ability of protein kinase-encoding oncogenes to also induce metastatic potential. In addition, the ability of ras to induce metastasis may be dependent on the regulation of its activity by other genes. Furthermore, transformation does not occur as an isolated genetic event, but is rather the result of interaction of two or more oncogenes. We suggest that the nature of these gene interactions will ultimately determine whether a cell is a benign transformant or a malignant and metastatic cancer.
Invasion Metastasis 1989
PMID:Oncogenes and metastatic progression. 268 84

Expression of the ras oncogene product p21 (ras p21) in benign and malignant human colonic tissues was studied using the monoclonal antibody RAP-5 and the avidin-biotin-peroxidase technique. Histologically normal colonic mucosa and hyperplastic mucosa adjacent to carcinomas (transitional mucosa) were found, in most cases, to be negative for reactivity with the antibody or showed weak staining of a few epithelial cells. Similar findings were observed in hyperplastic and juvenile polyps. Of the 145 adenomas studied, 47 (32.4%) showed detectable levels of ras p21 expression. RAP-5 immunohistochemical staining was significantly associated with the degree of epithelial dysplasia (P less than 0.01) and the size of adenoma (P less than 0.05), but not with the histological type. Fifty-four of 70 primary adenocarcinomas (77.1%) were reactive with RAP-5 and usually demonstrated a higher percentage of stained cells and more intense cytoplasmic staining than that observed in adenomas. Although metastases often displayed a similar or even higher levels of ras p21 expression compared with the primary carcinomas, in 10 cases one or more metastatic lesions showed lower levels of ras p21. These results suggest that enhanced ras p21 expression may, at times, occur in the early stages of human colon carcinogenesis but are probably not associated with metastatic tumour progression.
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PMID:ras p21 oncoprotein expression in human colonic neoplasia--an immunohistochemical study with monoclonal antibody RAP-5. 304 43

A metastatic colony is the end result of a complex series of steps involving multiple gene products. In some cases, the augmented metastatic potential of certain tumour cells may be due to the increased expression of specific gene products which confer a selective advantage. Transfection of the c-Ha-ras oncogene into suitable recipient cells constitutes a powerful experimental model with which to identify putative gene products augmented in highly metastatic tumour cells compared to their non-metastatic counterparts. Transfection of the activated ras oncogene into 3T3 and 10T1/2 embryo fibroblasts, and adult rat fibroblasts, results in transformants which produce high numbers of spontaneous metastases in nude mice or syngeneic recipients. The ras oncogene will also increase the metastatic aggressiveness of murine tumours with low metastatic potential. However, the ras oncogene will not induce the metastatic phenotype in all recipient cells. Furthermore, specific genes such as adenovirus 2 E1A suppress the ability of ras to induce the metastatic phenotype. Natural 'suppressor' gene products may exist which render certain cells resistant to the induction of metastases by ras. Ras oncogene transfection induces the production of type IV collagenase, motility factors and growth factors. The ras oncogene therefore induces a cascade of gene functions leading to rapid progression to the metastatic phenotype. The mechanism of the induction probably involves complex interactions between the ras p21 product and multiple cellular gene products.
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PMID:Oncogene induction of metastases. 307 39

Various murine tumor cell lines with different metastatic capacities were tested in vitro for oncogene expression, especially of the p21-Ha-ras protein. Small differences were seen in the expression of several distinct oncogenes in the case of a high metastatic lymphoma variant (ESb) and its low metastatic parental line (Eb). In one instance we observed a 30-fold Ha-ras gene amplification in a metastasis-derived cell line from a spontaneous mouse mammary carcinoma. In spite of this amplification we did not find an increased p21 expression in these cells.
Clin Exp Metastasis
PMID:Oncogene expression in related cancer lines differing in metastatic capacity. 328 Jan 94

Expression of the cellular ras Mr 21,000 protein (p21) has been measured in tumors from breast cancer patients who at time of presentation had no evidence of metastatic disease. Western blotting analysis revealed that 37 of 54 (69%) tumors contained p21 levels 2- to 10-fold greater than those of control breast tissues. An excessive increase of p21 (5- to 10-fold over the control value) occurred more frequently in tumors of T3 and T4 stages [15 of 25 (60%)] than in tumors at T2 stage [6 of 29 (21%)], suggesting a correlation between advancement of disease and high p21 levels. p21 levels were positively related to the involvement of axillary lymph nodes at the time of primary treatment. As no correlations were detected between p21 levels and a gross pathological parameter, tumor grade, it is possible that p21 levels may reflect the degree of cellular malignancy. This is supported by data on tumor recurrence; 13 of 16 patients (81%) with tumors expressing low p21 levels were disease free for greater than or equal to 4 years after primary treatment, whereas only 5 of 9 patients (56%) with high p21 tumors remained disease free. These results suggested that a quantitative enhancement of p21 oncogene protein is associated with both the progression and prognosis of breast cancer.
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PMID:Prognostic significance of the expression of a ras protein with a molecular weight of 21,000 by human breast cancer. 330 76


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