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

Second-passage rat embryo cells were transfected with a neomycin resistance gene and the activated form of the c-Ha-ras I gene, or with these two genes plus the adenovirus type 2 E1a gene. Foci of morphologically transformed cells were observed in both cases; however, the frequency of transformation was at least ten times higher with two oncogenes than with the ras gene alone. All the transformed cell lines gave rise to rapidly growing tumors when injected subcutaneously into nude mice. All but one of the cell lines transformed by the ras oncogene alone formed metastatic nodules in the lungs of animals that had been injected subcutaneously with transformed cells. When transformed cells were injected intravenously, all the ras single-gene transformants gave rise to many metastatic lung nodules. In contrast, cell lines transformed with ras and E1a did not generate metastases after subcutaneous injection and gave rise to very few metastatic lung nodules after intravenous injection. These data demonstrate that a fully malignant cell with metastatic potential, as measured in an immunodeficient animal, can be obtained from early passage embryo cells by the transfection of the ras oncogene alone.
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PMID:Primary rat embryo cells transformed by one or two oncogenes show different metastatic potentials. 345 44

The protein product of the ras cellular oncogene(s) (p21) was assayed in primary breast carcinomas from two groups of patients who had different axillary lymph node status. Using an immunohistochemical assay, the intensity and percent of neoplastic cells demonstrating ras p21 antigen staining were significantly higher in the primary tumors from patients with lymph nodes positive (LN+) for malignancy (20 patients) compared with the lymph node negative (LNO) group (21 patients). The expression of p21 also correlated with tumor size. Age and estrogen receptor status did not influence p21 staining. The antigen expression of p21 was similar in intensity and distribution in the primary tumor and regional lymph node metastases. Enhanced expression of p21 in primary breast cancers that metastasize to regional nodes indicates that ras p21 may be a determinant of the malignant potential of breast cancer cells and may represent a new class of more biologically relevant tumor markers.
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PMID:Elevated ras oncogene expression correlates with lymph node metastases in breast cancer patients. 352 1

Oncogenes encoding serine/threonine or tyrosine kinases were introduced into the established rodent fibroblast cell line NIH 3T3 and tested for tumorigenic and metastatic behavior in T cell-deficient nude mice. Transforming oncogenes of the ras family were capable of converting fibroblast cell lines to fully metastatic tumors. Cell lines transformed by the kinase oncogenes mos, raf, src, fes, and fms formed experimental metastases and (in some cases) these genes were more efficient at metastatic conversion than a mutant ras gene. In contrast, cells transformed by either of two nuclear oncogenes, myc or p53, were tumorigenic when injected subcutaneously but were virtually nonmetastatic after intravenous injection. These data demonstrate that, in addition to ras, a structurally divergent group of kinase oncogenes can induce the metastatic phenotype.
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PMID:Transformation by oncogenes encoding protein kinases induces the metastatic phenotype. 365 11

The effects of expression of human c-myc and both mutated (T24) and normal forms of human Ha-ras-1 were studied in an aneuploid rat fibroblast line (208F). Mutated T24 Ha-ras was also studied in a near-diploid cell derived from early passage Chinese hamster lung fibroblasts (CHL). In contrast to the parental fibroblasts, cells expressing any of the human oncogenes engendered rapidly growing tumours in immune-suppressed animals. Blood- and lymph-borne metastases were observed from both ras- and myc-expressing cells. In general ras-expressing cells were more aggressive than those expressing myc. In the 208F background, expression of c-myc was associated with an incidence of mitosis similar to that in tumours expressing T24 Ha-ras, but incidence of single cell death by apoptosis was higher. Quantitatively, expression of human oncogene mRNA was constant during growth in vivo, and similar to that sometimes observed in human neoplasms. Of 9 endogenous proto-oncogenes, 7 showed no change in expression from the parental fibroblasts, but c-abl and c-fos were strongly expressed in all cells expressing human ras or myc. Thus these tumorigenic cells, although transfected with single human oncogenes, all expressed oncogenes with both nuclear- and membrane-associated products.
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PMID:Rodent fibroblast tumours expressing human myc and ras genes: growth, metastasis and endogenous oncogene expression. 366 73

The hypothesis of tumor progression proposed by Nowell [P. C. Nowell, Science (Wash. DC), 194: 23-28, 1976] states that one mechanism for the development of the metastatic phenotype could be the induction of chromosomal instability. We have developed a new experimental system for studying the induction of the metastatic phenotype using early passage fibroblasts which become metastatic in nude mice after transformation with the Harvey ras oncogene [R. J. Muschel et al., Am. J. Pathol., 121: 1-8, 1985; R. Pozzatti et al., Science (Wash. DC), 232: 223-227, 1986]. Since the early passage fibroblasts themselves are diploid, we reasoned that this might be a system in which karyotypic change after tumor formation or metastasis might easily be evaluated. Thus, we performed cytogenetic analysis on multiple metastases and tumors which had been derived from cells transformed with the cellular Harvey ras1 oncogene and compared their karyotypes. The karyotypes of the cells isolated from 5 tumors and 14 metastases were, as far as we could determine, identical to those of the injected cells. This could easily be evaluated because of the two clones studied one was diploid; the other has a trisomy of chromosome 4 without any other detectable abnormality. These results suggest that in this system using nude mice, selection for a necessary or even advantageous chromosomal aberration does not occur during tumor formation or metastasis. Furthermore, they indicate that the presence of the ras gene itself does not induce chromosomal rearrangements or aneuploidy and that a cell can be both tumorigenic and metastatic yet remain diploid.
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PMID:Karyotypic analysis of diploid or near diploid metastatic Harvey ras transformed rat embryo fibroblasts. 373 Oct 77

The analysis of 11 various oncogenes expression in different human tumors showed that each tumor is characterised by a specific functioning program of these genes. In 40-50% of tumors the oncogenes ras, fos and myc are expressed. All other oncogenes are either considered to be "silent" or are expressed only in few cases. The increased expression of sis and myb oncogenes is observed in metastases.
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PMID:[Transcription of cellular oncogenes in human tumors]. 377 91

To investigate the hypothesis that increased malignant potential correlates with increased genetic instability, we measured spontaneous mutation rates for the production of ouabain-resistant mutants in two benign (nonmetastatic) murine cell lines and their recently induced metastatic variants. Metastatic variants of the NIH 3T3 and CBA SP-1 cells were induced by transfection with the h-ras oncogene. Metastatic variants were also induced from the CBA SP-1 cell line by treatment with either 2'-deoxy-5-azacytidine or hydroxyurea. Mutation rates for the parent NIH 3T3 cells and their metastatic variants were less than 3 X 10(-8) variants per cell per generation, with no significant differences between them. Rates for the CBA SP-1 line and its variants ranged from 9 X 10(-9) to 8 X 10(-8) variants per cell generation, again without statistically significant differences. We conclude that in the cell lines studied the rate of spontaneous mutation for ouabain resistance was unrelated to the acquisition of the metastatic phenotype. This conclusion was based on the view that the generation of ouabain-resistant mutants is a reflection of the overall stability of the genome. Since the spontaneous mutation rate for ouabain resistance was unchanged in cells that had recently acquired the ability to metastasize, other genetic or epigenetic events were probably responsible for progression to the malignant (metastatic) phenotype.
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PMID:Metastatic potential and spontaneous mutation rates: studies with two murine cell lines and their recently induced metastatic variants. 377 33

Noninvasive, nonmetastatic BW5147 T-lymphoma cells were transfected with the activated human c-Ha-ras oncogene and were examined subsequently for the acquisition of invasive properties in vitro and of metastatic potential in vivo. It was found that several transfectants harboring the ras gene had become invasive in vitro, as assessed in hepatocyte cultures, and metastatic after tail vein injection into syngeneic AKR mice. The induced level of both invasive and metastatic potential appeared to depend on the level of expression of the transfected ras gene. Those transfectants exhibiting an elevated level of ras expression, mostly cells containing a high copy number of the ras gene, showed the highest invasiveness (up to 30-fold increase) and produced widespread metastasis in all mice tested. Transfectants with a low level of ras expression were less invasive and formed metastases in a few mice only, limited to a few organs or even to a single deposit in one organ. Untransfected BW cells, control transfected cells without the ras gene, and ras transfectants that did not express the gene were noninvasive and nonmetastatic. No changes in number of ras gene copies were found between isolated metastases and the transfectants from which they were derived. However, RNA analysis of the cells from the isolated metastases revealed similar, as well as elevated or diminished levels of ras transcription when compared to the corresponding cell lines prior to injection, suggesting that a persistent high expression of the ras gene is not necessarily needed for the independent growth at the secondary site. Our results indicate that the activated human ras oncogene may confer metastatic potential onto lymphoid tumor cells, probably due to the induction of invasiveness.
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PMID:Invasive and metastatic potential induced by ras-transfection into mouse BW5147 T-lymphoma cells. 380 80

NIH 3T3 mouse fibroblasts form nonmetastasizing fibrosarcomas upon transformation by the Ha-ras oncogene isolated from the EJ human bladder carcinoma cell line and subcutaneous inoculation into immunocompetent NFS/NCr mice. DNA from a human metastatic tumor was transfected into these Ha-ras transformants, and one of the resulting colonies yielded a lung metastasis after subcutaneous inoculation. DNA was isolated from this metastasis and subjected to a second round of transfer into Ha-ras-transformed NIH 3T3 cells. Inoculation of these transfected cultures into mice led once again to formation of metastases, this time at a higher frequency. Examination of four of the resulting metastases revealed discrete human DNA fragments that were common to all four. These findings demonstrate that the metastatic phenotype can be transferred via DNA from cell to cell and is associated with the presence of a discrete DNA segment. This segment is not identical to the myc oncogene or to any of the frequently detected ras tumor oncogenes.
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PMID:Expression of the metastatic phenotype in cells transfected with human metastatic tumor DNA. 385 54

Activation of the cellular oncogene ras has been implicated in many types of human malignancies. In this study, the relative levels of p21 protein product of ras (p21ras) in primary and metastatic colon tumors were compared to those in adjacent normal tissues. Nine of the 17 primary tumors had substantially elevated levels of p21ras with respect to adjacent normal tissues. Eight of these tumors were from Dukes' B and C stages. Four of the five tumors classified as "D" stage (in which distant metastases are present) did not show elevated levels of p21ras. In metastases from primary colon tumors, nine of nine were considerably reduced in p21ras expression regardless of the site of metastasis. These data suggest that elevation of p21ras may be a common event in early stages of colon tumors, and tumor progression may lead to a more autonomous population of cells in which other growth factors supplant the role of this protein.
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PMID:Expression of p21ras in fresh primary and metastatic human colorectal tumors. 388 18


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