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)

Our previous studies have shown that DNA from some human skin cancers contained activated Ha-ras oncogenes capable of inducing tumorigenic transformation when introduced into NIH 3T3 cells by DNA-mediated gene transfer. In addition, we found that NIH 3T3 cells transfected with DNA from one of the human skin cancers not only induced s.c. tumors at the site of injection but also metastasized spontaneously to the lungs in 100 per cent of nude mice injected. In this present study we examined the relationship between Ha-ras oncogene amplification and metastatic potential in tumors induced by various human skin cancer DNA-transfectants. Total cellular RNA was extracted from nude mouse tumor cell lines and analyzed by northern blot hybridization to a 32P-labeled, nick-translated Ha-ras probe. The metastatic potential of nude mouse tumor cell lines was assessed by their ability to form lung colonies after i.v. or s.c. injection. It was found that only the tumors expressing high levels of Ha-ras gene transcripts induced spontaneous metastasis after s.c. injection. There appeared to be little correlation between the level of Ha-ras oncogene amplification and experimental metastasis. These results suggest that amplification and overexpression of Ha-ras oncogene may play a role in the escape of cells from the primary tumor rather than in the ability of cells to survive in the circulatory system and colonize secondary sites.
Clin Exp Metastasis
PMID:Correlation between Ha-ras gene amplification and spontaneous metastasis in NIH 3T3 cells transfected with genomic DNA from human skin cancers. 264 32

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

Although tumors are often characterized as being the result of uncontrolled proliferation, clinically the morbidity from cancer results from its ability to invade and metastasize and to become resistance to our current therapeutic modalities such as chemotherapy and radiation. The study of oncogenes has largely stressed their ability to alter cell growth, but in fact they also influence these crucial features of tumor progression. In this review, we will summarize the data from our laboratory that indicated that the ras oncogene can induce metastasis as well as tumorigenicity and that the ras oncogene can also influence the development of radiation resistance. We have found that these changes in cells are sometimes accompanied by characteristic non-random chromosomal alterations in the transformed cells and will speculate that these accompanying chromosomal changes also may contribute to the features of tumor progression.
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PMID:Oncogenes and tumor progression. 268 35

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

We have used polymerase chain reaction (PCR), an amplification procedure, and oligonucleotide hybridization to detect ras gene point mutations in DNA from melanoma tumor samples. Genomic DNA was examined from 40 specimens of melanotic lesions, including benign nevi, primary melanomas, lymph node metastases, and systemic metastases. Adjacent normal skin or peripheral blood was analyzed as control material in 28 cases. ras mutations were detected overall in 25% of malignant tumors. In addition, mutations of all three ras genes were detected. We observed ras mutations in 2 of 4 benign atypical nevi (2 X K12), 4 of 22 primary melanomas (3 X K12, 1 X H12, 1 X N61), and 4 of 14 secondary (5 X K12, 1 X N61) tumors. One with a primary melanoma had concurrent K12 and H12, and two patients with secondary tumors had concurrent K12/N61 and K12 Asp/K12 Val mutations, respectively, making a total of 10 of 40 (25%) patients with ras mutations. This is the first demonstration of K-ras mutations in human melanoma. The presence of K-ras mutations in nevi, putative melanoma precursors, suggests that ras activation may be an early event in melanoma development. No correlation between tumor thickness and the presence of a ras mutation was observed.
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PMID:ras mutations in human melanotic lesions: K-ras activation is a frequent and early event in melanoma development. 269 57

Several classes of oncogenes were tested for their ability to confer cellular growth autonomy and the metastatic phenotype on CCL39 lung fibroblasts. v-sis as well as highly but not weakly expressed activated ras, v-fps and myc genes were susceptible to relieve CCL39 cells from their dependence on exogenous growth factors. However, based on growth rate estimations, ras and fps cells divided 2 to 3 times more rapidly than myc and sis cells in serum-free medium. All ras and fps cells produced pulmonary metastases in 60-100% of young nude mice, following subcutaneous or intravenous injection. Acquisition of factor-independent growth during in vivo passage was demonstrated in two instances. Animals developed either no or sporadic metastases after implantation of transfected cells expressing v-sis, normal Ha-ras, myc or no foreign oncogene. The results are consistent with the notion that the rate at which tumor cells can proliferate independently from growth factor stimulation is a good predictor of their metastatic potential. Oncogenes such as activated ras and fps appear more efficient than myc and sis to induce the metastatic conversion of preneoplastic CCL39 cells and to abrogate Go-arrest controls of division.
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PMID:Metastatic conversion of factor-dependent lung fibroblasts (CCL39) requires over-expression of oncogenes which induce high rate of autonomous replication. 275 2

Cancer invasion and metastases is a complex multi-step process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA in a variety of human carcinoma cells correlated with the number of laminin receptors on the surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases by employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor, resulting in a profound (greater than 100 x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.
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PMID:Biochemical mechanisms of tumor invasion and metastasis. 283 60

Cancer invasion and metastases is a complex multistep process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA is a variety of human carcinoma cells correlated with the number of laminin receptors on the cell surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor resulting in a profound (greater than 100x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.
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PMID:Biochemical mechanisms of tumor invasion and metastases. 283 81

Specific genetic alterations are observed in human breast cancer, but little is known about when these occur in the evolution of the disease. Three breast cancer effusions that occurred sequentially in a single patient were examined. Common cytogenic abnormalities were found in all effusion samples suggesting a single progenitor metastatic cell. Only the last effusion, however, exhibited a mutation of the c-K-ras gene and a loss of heterozygosity at the c-H-ras locus. These specific genetic abnormalities detected in the last effusion was correlated with improved in vitro growth of the primary cells, and with the ability to establish breast cancer cell lines. Thus a mutant ras gene and the loss of heterozygosity at the c-H-ras locus were associated with a more aggressive tumor phenotype occurring late in the course of this patient's disease and not with the initiation of the primary breast cancer, or in the establishment of metastases.
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PMID:Molecular lesions involved in the progression of a human breast cancer. 284 43

Cancer invasion and metastases is a complex multistep process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA is a variety of human carcinoma cells correlated with the number of laminin receptors on the cell surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor resulting in a profound (greater than 100x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.
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PMID:Biochemical mechanisms of tumor invasion and metastases. 285 25


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