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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer-associated DNA hypomethylation is as prevalent as cancer-linked hypermethylation, but these two types of epigenetic abnormalities usually seem to affect different DNA sequences. Much more of the genome is generally subject to undermethylation rather than overmethylation. Genomic hypermethylation in cancer has been observed most often in CpG islands in gene regions. In contrast, very frequent hypomethylation is seen in both highly and moderately repeated DNA sequences in cancer, including heterochromatic DNA repeats, dispersed retrotransposons, and endogenous retroviral elements. Also, unique sequences, including transcription control sequences, are often subject to cancer-associated undermethylation. The high frequency of cancer-linked DNA hypomethylation, the nature of the affected sequences, and the absence of associations with DNA hypermethylation are consistent with an independent role for DNA undermethylation in cancer formation or tumor progression. Increased karyotypic instability and activation of tumor-promoting genes by cis or trans effects, that might include altered heterochromatin-euchromatin interactions, may be important consequences of DNA hypomethylation which favor oncogenesis. The relationship of DNA hypomethylation to tumorigenesis is important to be considered in the light of cancer therapies involving decreasing DNA methylation. Inducing DNA hypomethylation may have short-term anticancer effects, but might also help speed tumor progression from cancer cells surviving the DNA demethylation chemotherapy.
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PMID:DNA methylation in cancer: too much, but also too little. 1215 3

The expression of human papillomavirus (HPV) E6 oncoprotein is causally linked to high-risk HPV-associated human cancers. We have recently isolated hADA3, the human homologue of yeast transcriptional co-activator yADA3, as a novel E6 target. Human ADA3 binds to the high-risk (cancer-associated) but not the low-risk HPV E6 proteins and to immortalization-competent but not to immortalization-defective HPV16 E6 mutants, suggesting a role for the perturbation of hADA3 function in E6-mediated oncogenesis. We demonstrate here that hADA3 directly binds to the retinoic X receptor (RXR)alpha in vitro and in vivo. Using chromatin immunoprecipitation, we show that hADA3 is part of activator complexes bound to the native RXR response elements within the promoter of the cyclin-dependent kinase inhibitor gene p21. We show that hADA3 enhances the RXR(alpha)-mediated sequence-specific transactivation of retinoid target genes, cellular retinoic acid-binding protein II and p21. Significantly, we demonstrate that E6 inhibits the RXR(alpha)-mediated transactivation of target genes, implying that perturbation of RXR-mediated transactivation by E6 could contribute to HPV oncogenesis.
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PMID:Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator. 1223 59

Serological analysis of cDNA expression library (SEREX) was employed to identify cancer-associated genes. By screening cDNA expression libraries with sera of patients with lung cancers, we identified a total of 49 genes that specifically reacted with the sera of patients with lung cancers. Among these, we characterized a novel gene with expression pattern similar to that of cancer/testis antigens. Its open reading frame is 1920 bp in size and encodes for putative protein composed of 639 amino acids. Southern blot analysis reveals that this gene exists as single copy. In vitro transcription/translation and Western blot analysis confirm that this gene encodes a protein of 73 kDa in size. The comparison of cDNA and genomic sequences reveals that it is composed of 11 exons and 10 introns. This gene displays testis-specific expression among normal tissues, and wide expression among various cancer tissues and cancer cell lines. A study using GFP fusion construct reveals mainly nuclear localization of CAGE-1 protein. The expression of this clone is relatively higher in cancer tissues compared with their surrounding non-cancerous tissues. This suggests that overexpression of CAGE-1 may be associated with the progression of tumor. Because of its association with cancer, this gene was named cancer-associated gene-1 (CAGE-1). Given the fact that several cancer/testis antigens reportedly induce cytolytic T lymphocyte (CTL) reactions, it is reasonable that this gene will be a valuable target for cancer immunotherapy. The exact functional role of CAGE-1 in tumorigenesis remains to be seen.
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PMID:Identification and characterization of a novel cancer/testis antigen gene CAGE-1. 1253 76

Engineering cancer-associated mutations into the mouse germline is an important tool for biological studies of growth control and tumorigenesis. Tractable models of many human cancers now exist in which the initiating genetic lesions have been elucidated and, in some instances, where the cooperating lesions are also known. The urgent need for more effective strategies for treating human cancer has stimulated interest in harnessing these models to test therapeutic agents. Although the ultimate value of genetically engineered mouse models for cancer drug discovery is unknown, several encouraging experiments provide proof of principle.
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PMID:Mouse cancer models as a platform for performing preclinical therapeutic trials. 1257 40

We report here a genome-wide analysis of alternative splicing in 2 million human expressed sequence tags (ESTs), to identify splice forms that are up-regulated in tumors relative to normal tissues. We found strong evidence (P < 0.01) of cancer-specific splice variants in 316 human genes. In total, 78% of the cancer-specific splice forms we detected are confirmed by human-curated mRNA sequences, indicating that our results are not due to random mis-splicing in tumors; 73% of the genes showed the same cancer-specific splicing changes in tissue-matched tumor versus normal datasets, indicating that the vast majority of these changes are associated with tumorigenesis, not tissue specificity. We have confirmed our EST results in an independent set of experimental data provided by human-curated mRNAs (P-value 10(-5.7)). Moreover, the majority of the genes we detected have functions associated with cancer (P-value 0.0007), suggesting that their altered splicing may play a functional role in cancer. Analysis of the types of cancer-specific splicing shifts suggests that many of these shifts act by disrupting a tumor suppressor function. Sur prisingly, our data show that for a large number (190 in this study) of cancer-associated genes cloned originally from tumors, there exists a previously uncharacterized splice form of the gene that appears to be predominant in normal tissue.
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PMID:Discovery of novel splice forms and functional analysis of cancer-specific alternative splicing in human expressed sequences. 1450 Aug 27

The association of chronic inflammation with a variety of epithelial malignancies has been recognised for centuries. Well established examples include, among many others, oesophageal adenocarcinoma associated with chronic oesophagitis and bowel cancer associated with chronic inflammatory bowel diseases. By now no data, other than clinical observation, have been available in understanding the pathogenesis of these inflammation-related tumours. However, recent molecular studies on the relationship between solid malignancies and the surrounding stroma have given new insights. There is now enough evidence to accept that the chronic inflammatory process per se is able to provide a cytokine-based microenvironment which is able to influence cell survival, growth, proliferation, differentiation and movement, hence contributing to cancer initiation, progression, invasion and metastasis. Here it is discussed whether also oral lichen planus (OLP), being a chronic inflammatory autoimmune disease which has been clinically associated with development of oral squamous cell carcinoma, might be categorised among these disorders. With this aim, we critically reviewed and detailed the presence, in OLP subepithelial infiltrate, of inflammatory cells and cytokine networks that might act to promote squamous tumorigenesis.
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PMID:Immune activation and chronic inflammation as the cause of malignancy in oral lichen planus: is there any evidence ? 1469 34

Ovarian carcinoma (OC) is a leading cause of death among women throughout the world. A number of cancer-associated genes have been shown to be inactivated by hypermethylation of CpG islands during tumorigenesis. We tested the hypothesis that methylation status of MGMT, CDH1, RAR-beta and SYK could be important in the ovarian tumorigenic process and can lead to the gene(s) inactivation. Therefore, we assessed the promoter hypermethylation of MGMT, CDH1, RAR-beta and SYK in 43 ovarian granulosa cell tumours (GCTs) (adult type) using methylation-specific PCR. These tumours are relatively rare, accounting for approximately 3% of all ovarian cancers. Hypermethylation of MGMT (in 14 tumours), CDH1 (in nine tumours), RAR-beta (in eight tumours) and SYK (in seven tumours) have been found. Selective loss of RAR-beta and RAR-beta2 mRNA has been found in seven patients, while that of MGMT and SYK in three patients who also show aberrant methylation in promoter region of RAR-beta in addition to MGMT, SYK and CDH1 genes. Promoter CpG hypermethylation may be an alternative to mutation(s) to inactivate tumour suppressor genes such as MGMT, CDH1, RAR-beta and SYK, and this can also be an early event in the pathogenesis of OCs. Moreover, hypermethylation of the MGMT and CDH1, MGMT and RAR-beta and CDH1 and RAR-beta promoters occurred concordantly (P< 0.001, 0.0421 and 0.0005 respectively; Fischer's exact test). In addition to this, monosomy 22 and trisomy 14 have also been found in 10 tumours. It is clear from the results that hypermethylation of the promoter region of these tumour suppressor genes, monosomy 22 and trisomy 14, may be critical steps in the tumorigenesis, which consequently play a permissive role for tumour aggressiveness. All these events might play an important role in the early clinical diagnosis of the disease. Our results, therefore, suggest a potential role for epigenetic modification of these critical tumour suppressor genes in pathways relevant to the transformation and differentiation of rare type of ovarian cancer (GCTs).
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PMID:Promoter hypermethylation of MGMT, CDH1, RAR-beta and SYK tumour suppressor genes in granulosa cell tumours (GCTs) of ovarian origin. 1497 Aug 67

The spectrum of human antigens allows a monitoring of various pathological processes such as autoimmune disorders and tumorigenesis. Serological analysis of cDNA expression libraries (SEREX) is now used to search for new cancer-associated antigens, which are potential diagnostic markers or targets for immunotherapy of cancer. The results obtained for several solid tumors are reviewed. Groups of antigens detectable by SEREX, causes of immunogenicity of autoantigens, and prospective implication of antigens in diagnostics and monitoring of cancer are discussed.
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PMID:[Serological study of a repertoire of human cancer antigens and autoantigens]. 1512 27

Telomeres are nucleoprotein complexes that cap the end of eukaryotic chromosomes. They are essential for the functions and the stability of the genomes. In the absence of telomerase, the enzyme that adds telomeric DNA repeats to chromosome ends, telomeres shorten with cell division, a process thought to contribute to cell senescence. Reciprocally, telomere stabilization in immortalized cells, that usually appears concomitant with detection of telomerase activity, suggests that telomerase is essential for unlimited cell proliferation. Sequential modifications in the function of telomeres play antagonistic functions as far as tumorigenesis is concerned. Telomere dysfunction is thought to promote genome instability at initial stages, favoring the emergence of cancer-associated chromosomal abnormalities; reestablishment of telomere maintenance is expected afterwards if efficient cell cycling is to occur.
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PMID:[The opposite roles of telomerase during initiation and progression of cancers]. 1536 58

Pre-mRNA processing is an important mechanism for globally modifying cellular protein composition during tumorigenesis. To understand this process during lung cancer, expression of two key pre-mRNA alternative splicing factors was compared in a mouse model of early lung carcinogenesis and during regenerative growth following reversible lung injury. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and alternative splicing factor/splicing factor 2 (ASF/SF2) act antagonistically to modulate splice site selection. Both hnRNP A1 and ASF/SF2 contents rose in adenomas and during injury-induced hyperplasia compared to control lungs, as measured by immunoblotting. While both proteins increased similarly during compensatory hyperplasia, hnRNP A1 increased to a much greater extent than ASF/SF2 in tumors, resulting in a 6-fold increase of the hnRNP A1 to ASF/SF2 ratio. Immunohistochemical analysis showed that hnRNP A1 localized exclusively within tumor nuclei, while ASF/SF2 appeared in cytoplasm and/or nuclei, depending on the growth pattern of the tumor cells. We also demonstrated cancer-associated changes in the pre-mRNA alternative splicing of CD44, a membrane glycoprotein involved in cell-cell and cell-extracellular matrix interactions. hnRNP A1 and ASF/SF2 expression is thus differentially altered in neoplastic lung cells by mechanisms that do not strictly arise from increased cell division. These changes are influenced by tumor histology and may be associated with production of variant CD44 mRNA isoforms.
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PMID:Relative amounts of antagonistic splicing factors, hnRNP A1 and ASF/SF2, change during neoplastic lung growth: implications for pre-mRNA processing. 1539 79


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