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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that second-passage rat embryo cells transformed by the ras oncogene alone are both tumorigenic and highly metastatic when injected into nude mice. In contrast, rat embryo cells cotransformed with the ras oncogene and the adenovirus type 2 (Ad2) E1a gene are tumorigenic but either fail to metastasize or exhibit a very low metastatic potential. In this report, we demonstrate that transfection of the Ad2 E1a gene into four independent ras-transformed rat embryo cell lines results in a dramatic reduction in metastatic potential relative to that of the parental cell line. Transfection of cDNAs for the 12S and 13S E1a transcripts showed that the 12S cDNA was highly effective in reducing the metastatic potential of ras-transformed cell lines, while the 13S cDNA showed an effect in only one of the two cell lines tested. This effect is specific to the Ad2 E1a gene, since ras-transformed cell lines expressing the Ad12 E1a gene maintained their high metastatic potential. We hypothesize that the Ad2 E1a gene may regulate the expression of one or more cellular genes that contribute to the metastatic phenotype.
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PMID:The E1a gene of adenovirus type 2 reduces the metastatic potential of ras-transformed rat embryo cells. 297 8

We have previously demonstrated that rat embryo cells transformed by the ras oncogene alone are both tumorigenic and highly metastatic when injected into nude mice. In contrast, rat embryo cells transformed with the ras oncogene and the adenovirus 2 (Ad2) Ela gene are tumorigenic but either fail to metastasize, or exhibit a very low metastatic potential. Here we demonstrate that transfection of the Ad2 Ela gene into several of the ras transformed rat embryo cell lines results in a dramatic reduction in metastatic potential relative to the parental cell line. Transfection of cDNAs for the 12S and 13S Ela transcripts showed that both gene products are capable of reducing the metastatic potential of the ras transformed cell lines, however the 12S cDNA was more effective. This effect is specific to the Ad2 Ela gene as ras transformed cell lines expressing the Ad12 Ela gene or the human N-myc gene maintained their high metastatic potential. We hypothesize that the Ad2 Ela gene may regulate the expression of one or more cellular genes that contribute to the metastatic phenotype.
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PMID:Regulation of the metastatic phenotype by the E1A gene of adenovirus-2. 297 15

Activated c-Ki-ras with a point mutation (GGT to CGT) at codon 12, resulting in the substitution of arginine for glycine, was found in DNA from metastatic pancreatic adenocarcinoma in a lymph node. By means of restriction endonuclease length polymorphism with SacI digestion, we were able to demonstrate that the same point mutation of c-Ki-ras was present in the primary tumor and in metastases in lymph nodes. DNA from the normal spleen of the patient did not have this type of point mutation. Moreover, amplifications of 3- to 6-fold of the activated c-Ki-ras and 50-fold of c-myc were found in the primary tumor and the metastases in the two lymph nodes, indicating that point mutation had occurred at a relatively early stage of the tumor development, before amplification of the gene. This is the first clear demonstration of amplification of activated c-Ki-ras accompanied by amplification of c-myc in both primary and metastatic human tumors in vivo.
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PMID:Amplifications of both c-Ki-ras with a point mutation and c-myc in a primary pancreatic cancer and its metastatic tumors in lymph nodes. 300 77

Activated ras oncogene transfection into suitable recipient cells has been shown to induce the metastatic phenotype (Thorgeirsson, et al., Mol. Cell. Biol., 5: 259-262, 1985). We have used this model system to study the correlation of basement membrane collagenolysis with metastatic propensity. The c-Ha-ras oncogene alone, or combined with v-myc, transfected into early passage rat embryo fibroblasts, induce these cells to secrete high levels of type IV collagenolytic metalloproteinase and to concomitantly exhibit a high incidence of spontaneous metastases in nude mice. Cotransfection of c-Ha-ras plus the adenovirus type 2 E1a gene yields cells which are highly tumorigenic but nonmetastatic and fail to produce type IV collagenase. This effect is due to a suppression of collagenase elaboration, not increased production of a collagenase inhibitor, and not decreased production of a collagenase activator. The characteristics of the collagenase are identical to tumor type IV collagenase described previously. The nonmetastatic cells which failed to produce type IV collagenase retain the ability to secrete high levels of plasminogen activator. Transfection with the protooncogenic forms of Ha-ras or mos, or spontaneous transformation of NIH 3T3 cells or chemical transformation of BALB 3T3 cells yields cells which fail to produce collagenase, are tumorigenic, but totally nonmetastatic. These data support a biochemical linkage of type IV collagenase expression with the metastatic phenotype in this rodent system.
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PMID:Secretion of type IV collagenolytic protease and metastatic phenotype: induction by transfection with c-Ha-ras but not c-Ha-ras plus Ad2-E1a. 302 10

Messenger RNA levels of the c-fos, c-myc, c-Ha-ras and c-Ki-ras genes were studied in 39 tissue samples obtained from 17 patients undergoing surgery for colon carcinoma and other colon diseases. DNA extracted from the same samples was studied by Southern analysis. The tissues were tumors and grossly normal mucosa from each case and in some instances benign polyps and metastases. Our results indicate: (1) that 50% of cases studied show an increase in expression of at least one of the oncogenes studied; (2) that over-expression is not random, some cases over-expressing several of the genes studied; (3) that the expression pattern of the oncogenes studied varies between primary tumor and metastases; (4) that amplification is a rare event, being limited to one instance in which c-myc was amplified in a metastasis; (5) that cases which exhibit high levels of mRNA in one or more genes studied correlate with biologically aggressive tumors; and (6) that "non-expressors" are at higher risk for local recurrence based on correlations with mucin histochemistry.
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PMID:Prognostic implications of expression of the cellular genes myc, fos, Ha-ras and Ki-ras in colon carcinoma. 304 May 97

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

The development of metastatic ability by cancer cells is a multifactorial process whose temporal events are complex and poorly understood. One step in the metastatic process may involve cell motility. Previous studies reported correlations between motility and metastatic ability. Whether this correlation, seen in cancer cells maintained for long periods of time, is an epiphenomenon developing late in the growth of the cancer as a selection artifact of continuous passage, or is critically required for the acquisition of metastatic ability is unknown. To investigate the relationship between cell motility and the acquisition of metastatic ability, advantage was taken of recently developed DNA transfection methods for inducing high metastatic ability in initially low metastatic cancer cells. The Dunning AT2.1 cell line, a clonal rat prostatic cancer cell line with low metastatic ability, was transfected with a plasmid containing the neomycin resistance gene alone or in combination with the v-Harvey-ras oncogene. A series of the transfected cells was isolated by limiting dilution. After the first in vitro passage following transfection, cells were inoculated into rats to characterize their metastatic ability. The same transfectants were simultaneously studied using our visual grading system of cell motility to study the early motility changes associated with newly acquired metastatic ability. The data demonstrate increased membrane ruffling, pseudopodal extension, and cell translation (translocation) in the v-H-ras-transfected cell lines with high metastatic potential.
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PMID:Early cell motility changes associated with an increase in metastatic ability in rat prostatic cancer cells transfected with the v-Harvey-ras oncogene. 304 53

To investigate the role of oncogenes in the development of metastatic ability by prostatic cancer, the viral-Harvey-ras (v-H-ras) oncogene was introduced into the Dunning rat prostate adenocarcinoma cell line, AT2.1 by means of DNA transfection. The AT2.1 cell line is a cloned cell line that is anaplastic, rapidly growing, and has low metastatic potential; after subcutaneous (s.c.) inoculation in syngeneic rats, fewer than 10% of inoculated rats develop distant metastases. Calcium phosphate mediated DNA transfections of AT2.1 cells were performed with the v-H-ras oncogene or with control DNA. The in vitro growth rate of cloned transfectants, which contain and express the v-H-ras oncogene is similar to that of untransfected AT2.1 cells and of control transfectants. After s.c. inoculation in syngeneic rats, all transfectants produced rapidly growing tumors with similar growth rates. While control transfectants had low metastatic ability comparable to untransfected AT2.1 cells, the H-ras expressing transfectants metastasized in over 80% of inoculated rats. While the mechanism by which nonmetastatic Dunning tumor sublines spontaneously develop high metastatic ability in vivo during serial s.c. passage has not been addressed in the present studies, these studies do demonstrate that expression of an activated H-ras oncogene can reproducibly convert a tumorigenic nonmetastatic prostatic cell line to a highly metastatic state.
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PMID:Expression of a transfected v-Harvey-ras oncogene in a Dunning rat prostate adenocarcinoma and the development of high metastatic ability. 305 38

Metastasis formation is a multistep process that probably requires a complex interplay of a large and heterogeneous group of genes, including genes involved in cellular resistance to immunorejection and genes controlling the invasive potential of cells. Transfection experiments have shown that oncogenes of the ras gene family as well as oncogenes of the kinase group are able to induce invasive and metastatic properties in non-transformed cells as well as in tumorigenic, but non-metastatic, cells. However, these findings are not in agreement with observations on spontaneous human tumours in which no correlation was found between activation or increased expression of ras genes and the invasive and metastatic properties of these cells. Further studies have indicated that in particular cell types nuclear oncogenes like N-myc and adenovirus derived E1A may influence metastasis formation by trans-regulation of other genes, including class I genes of the major histocompatibility complex and genes coding for proteolytic enzymes. The many efforts to identify additional invasion and metastasis associated genes by transfection of high molecular weight metastatic tumour DNA met with little success. Somatic cell fusion studies, however, indicate that such genes exist and that one or more of them are located on human chromosome 7.
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PMID:Genetic analysis of invasion and metastasis. 307 71

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


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