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)

In order to evaluate the relevance of protooncogene alterations in gastric cancer and to specifically relate these alterations to types and stages of the neoplasia, we studied oncogenes of possible interest in gastric tumors with different clinical parameters. Fifty DNAs from primary gastric adenocarcinoma were analyzed, by the Southern blotting technique, for the presence of amplification or rearrangements of seven different protooncogenes: c-myc, c-erbB2, c-Ki-ras, c-Ha-ras, c-N-ras, hst, and c-mos. All the tumors analyzed were histologically classified and staged. Amplification of the following genes was found: c-myc (2 of 50), hst (3 of 50), c-erbB2 (3 of 50), and c-Ki-ras (5 of 50). The simultaneous amplification of hst (3 cases), c-myc (1 of 3), or c-Ki-ras (2 of 3) was observed. Analysis of DNAs from atrophic and metaplastic gastric mucosa (which can be regarded as preneoplastic lesions) of the 10 patients showing gene amplification demonstrated that this was limited to neoplastic cells. Considering protooncogene amplification in general (i.e., involving different genes and occurring to different degrees) and clinical parameters of tumors, we found a statistically significant association between amplification and both tumor progression and presence of metastases. Therefore, at least for the genes analyzed, amplification is a relatively infrequent phenomenon and represents a late event in the temporal development of gastric cancer.
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PMID:Heterogeneous protooncogene amplification correlates with tumor progression and presence of metastases in gastric cancer patients. 225 24

Carcinogen-induced point mutations resulting in activation of ras oncogenes have been demonstrated in various experimental systems such as skin carcinogenesis, mammary, and liver carcinogenesis. In many cases, the data support the conclusion that these point mutations are critical changes in the initiation of these tumors. The Syrian hamster embryo (SHE) cell transformation model system has been widely used to study the multistep process of chemically induced neoplastic transformation. Recent data suggest that activation of the Ha-ras gene via point mutation is one of the crucial events in the transformation of these cells. We have now cloned the c-Ha-ras proto-oncogene from SHE cDNA-libraries, and we have performed polymerase chain reaction and direct sequencing to analyze tumor cell lines induced by different chemical carcinogens for the presence of point mutations. No changes were detectable at codons 12, 13, 59, 61, and 117 or adjacent regions in tumor cell lines induced by diethylstilbestrol, asbestos, benzo(a)pyrene, trenbolone, or aflatoxin B1. Thus, it is not known whether point mutations in the Ha-ras proto-oncogene are essential for the acquisition of the neoplastic phenotype of SHE cells. Activation of other oncogenes or inactivation of tumor suppressor genes may be responsible for the neoplastic progression of these cells. However, in SHE cells neoplastically transformed by diethylstilbestrol or trenbolone, a significant elevation of the c-Ha-ras expression was observed. Enhanced expression of c-myc was detected in SHE cells transformed by benzo(a)pyrene or trenbolone.
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PMID:Activation of cellular oncogenes by chemical carcinogens in Syrian hamster embryo fibroblasts. 227 11

We examined the pattern of expression of several proto-oncogenes during nonneoplastic growth and in acinar cell neoplasms in the rat pancreas. The levels of c-myc, c-raf-1, and c-Ki-ras mRNAs were increased in regenerating pancreata following surgical partial pancreatectomy and following administration of camostat. We also investigated proto-oncogene expression associated with the progression of pancreatic cancers in azaserine-treated rats. Injection of a single dose (30 mg/kg) of azaserine (O-diazoacetyl-L-serine) to 14-d-old rats leads to a variety of neoplastic lesions in the rat pancreas. Total RNA was isolated from lesions in various stages of tumor progression, including adenomas, carcinomas in situ, and invasive carcinomas. We observed increased expression of c-myc, c-raf-1, and c-Ki-ras in azaserine-induced adenomas and carcinomas. Actin expression was also increased in these tissues, whereas amylase expression was variable. However, when compared to the normal growing pancreas, the level of proto-oncogene expression in the adenomas and carcinomas was disproportionate to the degree of cellular division in those tissues. Thus, the alterations induced by azaserine apparently caused a deregulated increase in expression of cellular oncogenes associated with growth regulation.
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PMID:Expression of c-myc, c-raf-1, and c-Ki-ras in azaserine-induced pancreatic carcinomas and growing pancreas in rats. 227 33

A rearranged c-myc gene found in a human primary giant cell carcinoma of the lung was analyzed. The rearrangement was found in the region about 6 kilobase pairs upstream of the c-myc gene. The breakpoint was joined to a sequence carrying a Line 1 (L1) family member located on chromosome 8. This in vivo rearrangement of the c-myc gene specific to tumor cells may represent one mechanism of activation of a protooncogene during tumorigenesis or tumor progression in human cancer.
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PMID:Joining of the c-myc gene and a line 1 family member on chromosome 8 in a human primary giant cell carcinoma of the lung. 233 29

Expression of four oncogenes and two keratin genes was determined in rat tracheal epithelial cell lines derived from tracheal implants exposed in vivo to 7,12-dimethylbenz[a]anthracene. Cell lines were grouped into four stages of neoplastic progression based on phenotypic markers in order to correlate oncogene expression with stage of malignancy. Northern analysis of RNA revealed a significantly enhanced expression of the c-myc oncogene in the most tumorigenic or tumor-derived cell lines, whereas preneoplastic cells expressed approximately five-fold less transcript. Southern analysis of tracheal cell DNA did not demonstrate amplification of the c-myc gene in any of the positive cell lines. In contrast to c-myc, other oncogenes such as ras and fos were expressed in all cell lines, as well as in control cell cultures, to a similar extent. Patterns of differentiation were examined in these epithelial cell lines by determining the expression of two distinct keratin genes, KA-1 and KB-2. Both malignant and preneoplastic cells expressed the KB-2 gene at variably high levels, whereas the expression of the KA-1 keratin was barely detectable in any of the cell lines. The stage-specific expression of the c-myc oncogene in these tracheal cell lines suggests a correlation between the regulation of certain oncogenes and neoplastic progression in this model of respiratory carcinogenesis.
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PMID:Oncogene expression in cell lines derived from rat tracheal implants exposed in vivo to 7,12-dimethylbenz[a]anthracene. 248 55

The human breast cell line HBL100 acquires the capacity to invade normal tissues and to replace them by proliferation in vitro only at high passage levels (HPL). These cells therefore are a useful model for studying tumor progression in vitro. We have analyzed the expression of cell-surface markers supposed to be involved in the control of the neoplastic process. Quantitative flow cytometry has revealed that: (1) spontaneous expression of HLA class-I antigens strongly decreases in HPL HBL100 cells vs. LPL cells, which parallels amplification and over-expression of c-myc oncogene; (2) HLA DR antigens can be induced by IFN-gamma in LPL but not in HPL HBL100 cells; (3) HBL100 cells secrete a soluble protein factor which specifically inhibits HLA DR induction by IFN-gamma even in heterologous cell systems; (4) 50% of LPL HBL100 cells express integrin beta 3, whereas HPL HBL100 cells lose this antigen; (5) this cell line is myoepithelial in origin, since 100% of HBL100 cells exhibit the CD10 antigen. Our data stress a role of HLA antigens, of some integrins and of c-myc in the acquisition of malignant potential by myoepithelial mammary cells of the HBL100 line.
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PMID:Acquisition of tumorigenic potential in the human myoepithelial HBL100 cell line is associated with decreased expression of HLA class I, class II and integrin beta 3 and increased expression of c-myc. 249 51

In a small-cell lung carcinoma (SCLC) tumor specimen as well as in 3 cell lines derived from SCLC biopsies obtained from the same patient at successive times during the clinical course, either the N-myc gene or the c-myc gene appeared to be amplified and expressed. The initial tumor specimen, a lymph-node metastasis, was amplified for N-myc, as was the cell line GLC-14 derived from this metastasis. The cell lines GLC-16 and GLC-19, derived from the recurrent primary tumor biopsies after a complete remission, were amplified for c-myc. This finding implies independent amplification events and supports the idea that the amplification of myc genes is probably a secondary event correlated with tumor progression. Although all 3 cell lines could be classified as classic SCLC cell lines according to their histological characteristics, GLC-16 and GLC-19 clearly possess, in their c-myc amplification and derivation from therapy-resistant tumor cells, features of variant SCLC lines. This may question the significance of the classic/variant classification.
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PMID:Amplification and expression of different myc-family genes in a tumor specimen and 3 cell lines derived from one small-cell lung cancer patient during longitudinal follow-up. 254 36

We have examined avian leukosis virus-induced B-cell lymphomas for multiple, stage-specific oncogene activations. Three targets for viral integration were identified: c-myb, c-myc, and a newly identified locus termed c-bic. The c-myb and c-myc genes were associated with different lymphoma phenotypes. The c-bic locus was a target for integration in one class of lymphomas, usually in conjunction with c-myc activation. The data indicate that c-myc and c-bic may act synergistically during lymphomagenesis and that c-bic is involved in late stages of tumor progression.
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PMID:Multiple proto-oncogene activations in avian leukosis virus-induced lymphomas: evidence for stage-specific events. 254 84

The antitumor drugs mAMSA and VM26 were shown to stimulate the topoisomerase II (Topo II) cleavage activity on the c-myc protooncogene in several human tumor cell lines (N417, HL60, EJ, H146, CaSki, A431, IGROV1, and CAL18A) and human peripheral lymphocytes. The mAMSA-induced gene cleavage was found to increase with the steady-state levels of c-myc transcripts in cell lines while no cleavage could be evidenced in the other genes so far tested. In mAMSA-treated N417 cells, the overall genomic DNA cleavage detected by alkaline elution was found to be about 20 times lower than the c-myc gene cleavage. Topo II mRNA levels were associated with the nuclear Topo II decatenating activity in cell lines and increased with c-myc cleavage. Topo II decatenating activity was found to be 3 times lower in quiescent than in exponentially growing N417 cells, but the c-myc cleavage induced by mAMSA was found as intense in quiescent as in growing cells. Thus, our data seem to indicate that c-myc gene cleavage is not related to cellular Topo II content but rather to c-myc gene transcription. Therefore, we suggest that only a small fraction of the Topo II is able to react with drug on the c-myc gene in relation to its transcriptional accessibility. Since c-myc overexpression is frequently found to be related to human cancer progression, we suggest that this gene could be an important target for Topo II related antitumor drugs.
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PMID:Stimulation of the topoisomerase II induced DNA cleavage sites in the c-myc protooncogene by antitumor drugs is associated with gene expression. 255 17

Tumor progression usually involves a complex pattern of molecular alterations. In many human tumors oncogene amplification or activation has been associated with advanced stages of cancer. Transfection studies have demonstrated the ability of several cellular oncogenes to induce a more malignant phenotype in transformed cells. We have examined the role of c-myc in tumor progression in rat tracheal cell culture, and in rat skin tumors induced by ionizing radiation. In the latter in vivo model, c-myc amplification was found to occur as a function of tumor size. Serial biopsies of growing tumors confirmed the trend toward increased gene copy number with time and stage of progression. This effect was specific for the c-myc gene, in epithelial tumors. Evidence was found for a role of tumor heterogeneity and evolution of tumor cell subpopulations in determining the oncogene activation profile of individual tumors.
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PMID:An experimental model for oncogene activation during tumor progression in vivo. 268 38


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