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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The occurrence of different components of the cell growth regulation pathway as expressed in experimental skin carcinogenesis in haired carcinogen-sensitive NMRI, in haired carcinogen resistant DBA/2 mice and in hairless SKH/1 mice was studied by morphological and immunohistochemical methods. The results were compared with respect to neoplastic response, number of tumors, tumor behaviour and to the inducing agent (UV irradiation or chemical carcinogen), in order to increase our understanding of specific alterations in neoplastic development caused by extraneous agents and to determine their possible usefulness as indicators of carcinogen exposure. The expression of growth factors (transforming growth factor alpha and epidermal growth factor), growth factor receptors (epidermal growth factor receptor/c-erbB-1 and c-erbB-2/neu), cell signalling component c-myc, the nuclear transcription factor Harvey-Ras and the tumor suppressor gene p53, were studied in carcinogen- and UV-induced tumor formation in mouse. The results showed increased oncogene expression as well as growth factor expression in the skin during tumor development appearing early in neoplastic and premalignant conditions and becoming more distinct during neoplastic progression. Efforts to delineate specifically initiated cells prior to the appearance of morphologically detectable alterations including dysplasia, papilloma formation and squamous cell carcinomas, were unsuccessful. Increased staining by antibodies to growth factors and oncogenes were also observed in DBA/2 animals resistant to tumor formation. It is concluded that oncogene expression and growth factor protein deposits are associated with carcinogenic effects, partly explaining the mechanism of action of these agents, but the applicability, as such, for the analysis of potential hazardous agents needs further studies.
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PMID:Oncogenes and growth factors as indicators of carcinogen exposure. 867 68

Cancer of the esophagus exists in 2 main forms with different etiological and pathological characteristics-squamous cell carcinoma (SCC) and adenocarcinoma (ADC). This review focuses on the occurrence of genetic alterations in SSC and ADC of the esophagus and on their possible implications for the elucidation of the etiology and pathogenesis of these cancers. The most common alterations found in esophageal cancers include allelic losses at chromosomes 3p, 5q, 9p, 9q, 13q, 17p, 17q and 18q, as well as mutations of p53 (mostly missense), Rb (deletions), cyclin DI (amplifications) and c-myc (amplifications). The sequence of occurrence of these alterations with respect to histopathological tumor progression is discussed. Our findings underscore the different etiology and pathogenesis of SCC vs. ADC and suggest that the genetic alterations observed may represent molecular fingerprints of critical risk involved in the development of these 2 cancers.
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PMID:Genetic alterations in esophageal cancer and their relevance to etiology and pathogenesis: a review. 868 92

There is a direct correlation between the overexpression of the c-myc product and the clinicopathological state of patients with colorectal carcinomas. This study was carried out to understand the reasons for this. In vitro, S-phase synchronous culture was performed using the human colon carcinoma cell lines, COLO201 and SW480; and thymidine-hydroxyurea blockage was carried out. The proportion of c-myc protein-positive cells decreased gradually with progressive stage of the cell cycle, as determined by flow cytometry (FCM) and Western blot analysis. A rapid decrease in the number of c-myc protein-positive cells in the GO G1-phase was the main reason for the complete loss of c-myc protein expression in the S-phase of synchronous culture, although the percentage of these cells was higher in the S and G2M-phases than in the GOG1-phase after each initiation of synchronous culture. These findings suggest that the c-myc protein-positive cells which were arrested in the G1-phase could play an important role in cell proliferation. In another study, 46 paraffin-embedded specimens of human colorectal carcinomas were examined for c-myc protein expression by flow cytometry (FCM). Patients with higher expression in the GOG1-phase (% positive cells > or = mean) showed significantly lower rates of survival (p = 0.004), as determined using the generalized Wilcoxon's method, and this higher expression correlated with aneuploid carcinoma (p = 0.005), with metastasis to the lymph nodes (p = 0.003), with the degree of regional lymph node metastasis (p = 0.02), and with the depth of wall-infiltration by the carcinoma (p = 0.006), as determined using the chi square test. Liver metastases and peritoneal dissemination did not correlate with c-myc protein expression. Analyses of all phases were carried out, however, similar results were obtained by analyzing only the GOG1-phase of the cell cycle. Therefore, it would seem that determination of c-myc protein expression in a carcinoma, especially in the G1-phase of the cell cycle, would be useful as a marker of tumor progression and for evaluation of the clinical prognosis of patients with colorectal carcinomas.
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PMID:Correlation between c-myc protein expression and phases of the cell cycle in human colorectal carcinomas. 882 91

Recent investigations have demonstrated p53 and Rb alterations in a subset of transitional cell carcinoma (TCC). Further genetic changes during tumor progression include overexpression of the c-myc gene in a significant number of mainly invasive bladder tumors. To study the possible interactions between these genes in TCC, urothelial cancer cell lines were chosen as an in vitro model. Expression and mutation of p53 was studied in 15 bladder cancer cell lines by immunocytochemistry, Western blot, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing of double stranded PCR products of exons 4, 5, 7 and 8 of genomic DNA. C-myc expression and gene structure were studied using Northern and Southern blot techniques Rb protein expression was analyzed by Western blot. Twelve of 15 cell lines showed either p53 mutations or abnormal protein expression. Consistent with previous studies, five cell lines did not express Rb protein. None of the cell lines studied retained both tumor suppressor genes in a functional form. The c-myc gene appeared to be intact in all cell lines and copy numbers were close to normal. Northern analysis demonstrated that all cell lines expressed c-myc mRNA but evidence for altered regulation was found in at least two cell lines. Our data suggest that amplification or translocation are not the underlying mechanism for c-myc overexpression in urothelial tumors. No correlation between loss of Rb protein and c-myc expression was observed. The results presented here for the cell lines match well those obtained in vivo. Thus, these cell lines may provide a suitable model for further analysis of molecular alterations in urothelial cancer.
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PMID:Inactivation of tumor suppressor genes and deregulation of the c-myc gene in urothelial cancer cell lines. 883 85

There are three nearly ubiquitous genomic "imbalances" in prostate cancer cells: 1) loss of sequences from the short arm of chromosomes 8, 2) loss of sequences from the long arm of chromosome 13q, and 3) gain of sequences on the long arm of chromosome 8, particularly in advanced disease. Candidate tumor suppressor genes and oncogenes affected by this trio of consistent changes include the c-myc gene on chromosome 8q24, the RB gene at 13q14, and potentially multiple novel genes on the short arm of chromosome 8, with a gene located more proximally potentially involved in tumor initiation and a gene or genes located more distally involved in tumor progression. Loss of regions of chromosomes 2q, 5q, 6q, 7p and 7q, 9p, 10p and 10q, 16q, 17p and 17q, and 18q, and gain of regions of 1q, 2p, 3p and 3q, 7p and 7q, 11p, 17q, and Xq have also been detected in the range of 25-50% of tumors studied. Analysis of candidate tumor suppressor genes in these regions is still in its early stages. Similarly, potential oncogenes on a series of chromosomal arms which undergo frequent amplification remain essentially uncharacterized. The basic outline of the chromosomal aberrations in prostate cancer has been well established; the details of the story remain to be filled in. This paper reviews the advantages and disadvantages of various techniques for detection of genomic loss and gain in prostate cancer cells, and reviews published reports of loss and gain in prostate cancer, focusing primarily on reports using microsatellite analysis, Southern analysis, and comparative genomic hybridization. Fluorescence in situ hybridization (FISH) based analyses of selected regions are also reviewed.
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PMID:Review of allelic loss and gain in prostate cancer. 891 74

The bic locus is a common retroviral integration site in avian leukosis virus (ALV)-induced B-cell lymphomas originally identified by infection of chickens with ALVs of two different subgroups (Clurman and Hayward, Mol. Cell. Biol. 9:2657-2664, 1989). Based on its frequent association with c-myc activation and its preferential activation in metastatic tumors, the bic locus is thought to harbor a gene that can collaborate with c-myc in lymphomagenesis and presumably plays a role in late stages of tumor progression. In the present study, we have cloned and characterized two novel genes, bdw and bic, at the bic locus. bdw encoded a putative novel protein of 345 amino acids. However, its expression did not appear to be altered in tumor tissues, suggesting that it is not involved in oncogenesis. The bic gene consisted of two exons and was expressed as two spliced and alternatively polyadenylated transcripts at low levels in lymphoid/hematopoietic tissues. In tumors harboring bic integrations, proviruses drove bic gene expression by promoter insertion, resulting in high levels of expression of a chimeric RNA containing bic exon 2. Interestingly, bic lacked an extensive open reading frame, implying that it may function through its RNA. Computer analysis of RNA from small exon 2 of bic predicted extensive double-stranded structures, including a highly ordered RNA duplex between nucleotides 316 and 461. The possible role of bic in cell growth and differentiation is discussed in view of the emerging evidence that untranslated RNAs play a role in growth control.
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PMID:bic, a novel gene activated by proviral insertions in avian leukosis virus-induced lymphomas, is likely to function through its noncoding RNA. 903 77

The c-myc gene product is known to be involved in the regulation of cell proliferation and differentiation. Altered c-myc gene expression is a common event in a variety of tumors. This study was designed to investigate c-myc overexpression in transitional cell carcinoma (TCC). The first part was designed to investigate the frequency of c-myc overexpression in relation to tumor stage and tumor grade. A second set of experiments was directed at the mechanisms underlying c-myc overexpression in TCC. A total of 185 paraffin-embedded urothelial tissue specimens were investigated immunohistochemically for c-myc overexpression. A single case of overexpression (6%) was observed in normal urothelial tissue (n = 16). c-myc overexpression was also infrequent in carcinoma in situ (TIS) (7/39 = 18%). In contrast, papillary urothelial tumors (n = 65) yielded c-myc overexpression in 38 cases (58%). Investigation of infiltrating bladder tumors revealed c-myc overexpression in 56% of T1 tumors and 59% of muscle-infiltrating tumors. The staining pattern in multifocal tumors was heterogeneous in 10 of 18 cases. Similarly, only 12 of 28 patients with tumor recurrences showed the same c-myc staining pattern in the primary tumor and in tumor recurrences. c-myc overexpression did not correlate with tumor grade or tumor progression. Nevertheless, the high frequency of c-myc overexpression in urothelial carcinoma suggests an important role for this protein in urothelial carcinoma. Therefore, the mechanism underlying c-myc overexpression was further investigated in six bladder carcinoma cell lines. Southern blot experiments under standardized conditions showed no significant gene amplification. The comparison of c-myc mRNA expression to that of histone H3 as a measure of cell proliferation revealed a moderate correlation (r = 0.45) in the six cell lines examined. These data suggest that in accord with its established role as a cell cycle competence factor, c-myc may be necessary but not sufficient for the induction of proliferation in urothelial carcinoma.
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PMID:c-myc in bladder cancer. Clinical findings and analysis of mechanism. 907 56

Transforming growth factor beta-1 (TGF-beta1) is a potent inhibitor of hepatocyte growth both in vivo and in vitro. In this study, we analyzed the effects of TGF-beta1 on both naturally occurring and diethylnitrosamine-induced hepatocarcinogenesis using single transgenic TGF-beta1 and double transgenic c-myc/TGF-beta1 mice in which the expression of both transgenes was targeted to the liver. Hepatocellular tumors developed spontaneously in 59% (10 of 17) of the TGF-beta1 mice by 16-18 months of age. Coexpression of TGF-beta1 and c-myc transgenes in the liver accelerated hepatic tumor growth in both the presence and absence of carcinogenic treatment. Moreover, diethylnitrosamine-initiated tumors in the c-myc/TGF-beta1 mice showed a high rate of malignant conversion associated with a reduced expression or lack of TGF-beta receptor type II. The results suggest that overexpression of TGF-beta1 may contribute to liver carcinogenesis and that loss of TGF-beta receptor type II transduced inhibitory growth signals and up-regulation of c-myc are critical steps in liver tumor progression.
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PMID:Constitutive expression of mature transforming growth factor beta1 in the liver accelerates hepatocarcinogenesis in transgenic mice. 918

Burkitt's lymphoma (BL) cell lines carry a translocated c-myc gene and, in 60-80% of cases, exhibit mutations in the p53 tumor suppressor gene. We examined the potential role of the p53 gene in BL tumorigenicity using an in vitro assay that measures p53-dependent cell cycle arrest in the G1 phase of the cell cycle and an in vivo athymic murine model that detects differences in the tumorigenicity of BL cell lines. A highly significant inverse correlation was found between the ability of BL cells to arrest in G1 after irradiation and their tumorigenicity in athymic mice, consistent with the notion that loss of p53 function is associated with increased tumorigenicity. Inactivation of wild-type (wt) p53 function by expression of the human papillomavirus E6 protein in the AG876V BL cell line, which carries both wt and mutant p53 proteins, rendered the cell line significantly more tumorigenic in athymic mice. Transfection of the wt p53 gene into the p53 mutant and highly tumorigenic BL-41 cell line caused it to acquire wt p53 function and rendered it less tumorigenic in mice. In addition to confirming a role for the loss of p53 function in tumor progression, the data demonstrate that wt p53 protein can reduce BL tumorigenicity in vivo.
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PMID:Role of the p53 tumor suppressor gene in the tumorigenicity of Burkitt's lymphoma cells. 919 33

We compared the cytogenetic pattern of 20 different primary tumor cell cultures (PTCC) of renal cell carcinoma (RCC) to their cytokine secretion and oncogene expression. High secretion of IL-6 (gene locus on chromosome 7p21-p14) was correlated with the gain of an additional chromosome 7. Structural changes involving chromosome 5q22, the site of the GM-CSF gene, were matched with the high secretion of GM-CSF in PTCC. No such association was found for beta 2-microglobulin, TGF-beta 1, TNF-alpha, IL-8, and oncogenes, such as c-fos, c-myc, and pan-ras. Our approach may be useful in simultaneously analyzing several factors contributing to tumor progression and may contribute to understanding the multistep development of RCC.
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PMID:Comparison of cytogenetics, cytokine secretion, and oncogene expression in primary cultures of renal carcinoma cells. 926 Jun 6


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