Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

47 tumor samples, 45 of which were obtained at thoracotomy for non-small cell lung cancer were examined for mutational activation of the oncogenes H-ras, K-ras, and N-ras. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed. ras gene mutations were present in nine of 35 adenocarcinomas of the lung (all K-ras), in two of two lung metastases of colorectal adenocarcinomas (1 x K-ras, 1 x N-ras) and in one adenocarcinoma sample obtained at autopsy (H-ras). All K-ras and H-ras mutations were in either position 1 or 2 of codon 12, while the N-ras mutation was in position 2 of codon 61. The potential clinical significance of K-ras activation was analyzed using the combined results of this and of our earlier study (S. Rodenhuis et al., New Engl. J. Med., 317: 929-935, 1987). Lung adenocarcinomas with K-ras mutations tended to be smaller and were less likely to have spread to regional lymph nodes at presentation. With a median follow up of 10 months, survival data are still immature. None of six adenocarcinomas of nonsmokers had a K-ras mutation and only one of four who had stopped smoking more than 5 years before. We conclude that mutational K-ras activation is present in about a third of adenocarcinomas of the lung and that the mutational event may be a direct result of one or more carcinogenic ingredients of tobacco smoke. Studies involving larger numbers of patients are required to confirm the association of K-ras activation with smoking and the inverse relation with tumor progression.
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PMID:Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. 304 48

The expression of oncogenes plays a central role in the regulation of cell growth in normal and neoplastic tissue. Techniques developed recently (blot and in situ hybridization), enable the quantitative detection and topographical localization of oncogene expression at DNA and RNA level. In colonic adenomas and carcinomas and in non neoplastic mucosa of the large bowel, expression products of the oncogenes Ha-ras, Ki-ras, fos, and c-myc were detected. In most tumors a significant overexpression--as compared to the normal mucosa--of Ha-ras, Ki-ras, and fos mRNA was found. The overexpression of oncogenes, however, did not correlate with tumor progression, neither qualitatively nor quantitatively. According to recent studies (4, 7) it can be concluded, that the expression of the Ki-ras gene altered by a single point mutation, contributes significantly to the initiation and progression of epithelial neoplasias of the colon mucosa. It can be concluded, therefore, that the demonstration of oncogene expression products will play an important role in tumor diagnosis in the future.
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PMID:[Oncogene expression in colonic cancers]. 305 85

In this review, we first discuss some of the experimental parameters that need to be considered in assessing the contribution of various oncogenes to tumor metastasis. We discuss the requirement for a number of in vivo assays to measure different aspects of metastatic ability and we describe a novel metastasis assay, which we have developed, in the naturally immune-deficient chick embryo. Other factors capable of influencing the effects of oncogenes in experimental studies of metastasis, including oncogene activation and the differentiated status of the recipient cell, are also examined. We present some of our experimental results analyzing the ability of two oncogenes, src and ras, to convert cells to a metastatic phenotype. We speculate that a major mechanism by which some oncogenes promote metastatic ability is by subverting a signal transduction process, resulting in activation of a set of genes, some of which appear to promote metastatic ability. Finally, we discuss the need for additional information on the contributions of oncogenes to tumor progression and metastasis in both experimental systems as well as in clinical tumors.
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PMID:Oncogene transformation and the metastatic phenotype. 305 58

We have developed a cell system which utilizes the human teratocarcinoma cell line PA-1, from which we have characterized four stages of tumor progression. Soon after establishment in culture PA-1 cells revert and are no longer tumorigenic in athymic nude mice. Later, PA-1 cells as they are passaged in culture, become tumorigenic at passage 100. The transition from nontumorigenic to tumorigenic is the result of the biological effects of an activated N-ras oncogene and can be reproduced by transfection of the cloned oncogene into preneoplastic PA-1 cells. Certain preneoplastic cells (prior to passage 100) in this series are susceptible to transformation by single oncogenes while others are not. In studying the basis of this susceptibility to single oncogene induced transformation we have found that somatic cell hybrids between preneoplastic cells which can suppress ras-induced transformation and ras-transformed cells are non-tumorigenic. Therefore, we believe that the progression from ras suppressing to ras susceptibility may be due to the inactivation of a trans-dominant suppressor gene. Our system has identified at least three steps which lead to tumorigenicity; establishment of growth past senesence, activation of a ras oncogene, and inactivation of an oncogene suppressor function. Further genetic alterations are necessary for tumor dissemination and metastasis.
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PMID:PA-1, a human cell model for multistage carcinogenesis: oncogenes and other factors. 305 62

Steady-state levels of c-Ha-ras mRNA were measured in eight sublines of the Dunning R3327 rat prostatic adenocarcinoma. As a control, normal dorsal prostate tissue was studied. Increased expression of c-Ha-ras is associated with tumor progression in one lineage of the Dunning R3327 system (H to AT1 to MAT-Lu and MAT-Ly-Lu). Here ras mRNA increases as the tumor advances from androgen dependence and a high degree of differentiation to an anaplastic aneuploid phenotype with high metastatic potential. However, in the other Dunning lineage (H to HI to HI-F to AT3), expression of c-Ha-ras is variable and does not correlate with tumor progression. Immunocytochemistry showed that levels of the c-Ha-ras p21 protein paralleled steady-state mRNA levels in variants. Transfection assays, using NIH/3T3 cells, suggested that the ras loci were not activated in the R3327 tumors. Levels of c-Ki-ras mRNA were also measured in the Dunning tumors; these did not correlate with tumor progression in either lineage. Expression of N-ras mRNA was not detected in the Dunning tumors.
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PMID:Expression of ras proto-oncogenes in the Dunning R3327 rat prostatic adenocarcinoma system. 306 50

The transformation of a potentially neoplastic cell into an autonomous highly malignant and metastatic tumor cell involves a multifactorial cascade of events. This will eventually lead not only to the emergence of a tumor cell with an unlimited potential of replication, but more important will contribute to its ability to ignore and evade homeostatic immune and non-immune regulatory mechanisms. Specifically, those mechanisms which may restrict and direct its growth, dissemination, patterns of differentiation and interaction with the cellular and humoral factors comprising its environment. However, many different factors may contribute to a highly invasive and malignant phenotype. It is obvious that one should expect that a cardinal role should be assigned to alterations in those factors which contribute to the capacity of the malignant cells with its environment at the cell membrane level, which in turn is dependent on the concerted functional expression of specialized membrane associated components (i.e. receptors, cyto adhesion molecules (CAM's), histocompatibility antigens, GAP junction complexes, extracellular matrix components, etc.). In the present studies, we have investigated the contribution of three major factors, which maybe the cause or result of alterations at the level of the cell membrane: MHC encoded antigen expression, susceptibility to the cytolytic activity of NK cells and enhanced expression of the c-K-ras proto-oncogene, as to their development of metastatic capacity of a malignant cell. To address these questions, we used metastatic (IE7) and non-metastatic (IC9) variants of the murine 3-methylcholanthrene induced T-10 fibrosarcoma. Using this system, the following major conceptually important observations were made: A. The restoration by transfection of the expression of membrane associated H-2K encoded glycoproteins abrogates the metastatic capacity of the highly metastatic tumor cell clone, IE7, irrespective of the degree of susceptibility to NK or c-K-ras oncogene expression. This reduction in metastatic capacity is followed by a significant decrease in its tumorigenicity which is concomitant with its ability to induce in vivo potent H-2K restricted CTL's. These results clearly indicate that H-2K region encoded molecules play no apparent role in determining the susceptibility of tumor cells to NK cells, and yet their loss or aberrant expression is a cardinal event in tumor progression towards metastatic capacity, a fact which is supported by similar observations achieved in other murine models (18).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:NK sensitivity, H-2, c-K-ras proto-oncogene expression and metastases: analysis of the metastatic potential of H-2 gene transfected fibrosarcoma cells. 306 49

Medullary thyroid carcinoma (MTC) is an endocrine tumor of the thyroid C cells that expresses high levels of the neuroendocrine peptide hormone calcitonin. During tumor progression in the host, there is an apparent loss of differentiation in MTC cells that involves a consistent decrease in calcitonin content of the tumor cells associated with decreased expression of the calcitonin gene and/or changes in a mRNA alternative-processing pattern away from that characteristic of the parent thyroid C cell. We now report that introduction of the viral Harvey ras (v-Ha-ras) oncogene into cultured human MTC cells can reverse such changes in gene expression and can induce endocrine differentiation of the tumor cells. The expression of v-Ha-ras is associated with decreased cellular proliferation and DNA synthesis. There is a marked increase in the number of cytoplasmic secretory granules that are a classic feature of differentiated thyroid C cells. v-Ha-ras expression induces increased expression of the calcitonin gene and the processing of the primary gene transcript is shifted to favor calcitonin mRNA rather than calcitonin-gene-related peptide (CGRP) mRNA production. These studies with cultured human MTC cells provide a model system to study the role of Ha-ras and related genes in neuroendocrine differentiation. The findings suggest an important approach for identifying genes in solid tumors whose altered expression may play a role in the impaired maturational capacity characteristic of cancer cells during tumor progression.
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PMID:Introduction of v-Ha-ras oncogene induces differentiation of cultured human medullary thyroid carcinoma cells. 311 76

The expressions of epidermal growth factor (EGF), EGF receptor, transforming growth factor (TGF) alpha and c-Ha-ras p21 in human gastric carcinomas were studied immunohistochemically. Any of these four marker proteins from gastric tumor cells was closely correlated with the depth of tumor invasion. The incidences of cases with EGF or synchronous expression of TGF alpha and c-Ha-ras in metastatic tumors were significantly higher than those in primary tumors (p less than 0.05 or p less than 0.01). Patients with synchronous expression of EGF and its receptor or TGF alpha and ras p21 had a far poorer prognosis than those without such synchronous expression. These findings strongly suggest that the EGF-related growth factors, EGF-receptor and ras p21 mutually play an important role in tumor progression and could be useful as potential metastatic and/or prognostic markers for gastric carcinoma.
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PMID:[Growth factors as biological markers of malignancy]. 326 Apr 65

Samples of 37 fresh human ovarian tumor biopsies were screened to detect proto-oncogene amplification and ras mutations. Three samples showed c-K-ras2 amplification; none of the other oncogenes tested revealed any gene amplification. 5-, 25-, and 120-fold amplifications were assessed by dilution experiments and soft laser densitometry. Corresponding elevated levels of c-K-ras2 mRNA and p21 ras protein were found in the three tumors. Analysis by the polymerase chain reaction method to detect point mutations of codon 12 or codon 61 of Harvey-, Kirsten-, or N-ras showed only the wildtype sequence in all specimens. No correlation was found between ras activation and degree of tumor progression or histological subtype. DNA from one of the tumors with c-K-ras2 amplification proved to have high transforming activity in the NIH 3T3 tumorigenicity assay, but the transforming gene was not c-K-ras2.
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PMID:ras oncogene activation in human ovarian carcinoma. 328 94

We have surveyed a panel of induced murine lymphomas for c-ras gene mutations. The K-ras gene seems to be preferentially activated in our system, and there are at least two examples of concomitant K- and N-ras gene mutations in the same tumor. This indicates that in some cases additional ras mutations may contribute to tumorigenesis and is evidence for a role of ras activation in tumor progression.
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PMID:Concomitant K- and N-ras gene point mutations in clonal murine lymphoma. 329 Jun 53


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