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

Analysis of the restriction enzyme digests of total genomic DNAs from a broad spectrum of human cell lines and from individuals with different genetic backgrounds, by hybridization with a series of cloned human histone sequences, indicated restriction site polymorphisms (RSPs) for two adjacent human histone genes which reside on chromosome 1. In most cell lines and individuals examined we observed a single 2.05 kb H4 histone HindIII fragment and a 7.0 kb H3 histone HindIII fragment. In contrast, the polymorphisms were manifested as a 2.15 kb H4 HindIII fragment and a 9.1 kb H3 HindIII fragment. From population studies, we were able to show that there is no linkage disequilibrium between these two polymorphic restriction sites. Nor was there any apparent correlation between the presence of the H3/H4 histone polymorphisms and maintenance of the transformed karyotype, passage in culture, transformation or tumor progression. These chromosome 1 H3 and H4 histone gene polymorphisms are common in the American Black population and, in our survey of individuals, were not found in the American Caucasian population. Among the American Blacks studied, the frequency of the H3 HindIII(-) allele is 43% and of the H4 HindIII(-) allele 30%. In limited family studies, we were unable to detect recombination between these two physically linked alleles.
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PMID:Human histone gene organization. Identification of a histone gene polymorphism prevalent in a black population. 301 75

The organization and expression of human histone genes were examined in W138 normal human diploid fibroblasts, SV40 transformed W138 cells, A549 epithelial lung carcinoma cells, two adeno-carcinoma cell lines (LOVO and HT29) and three leukemia cell lines (HL60, KG1 and K562). Analysis of the restriction enzyme digests of total genomic DNAs by hybridization with a series of cloned human histone sequences indicated polymorphic organization of at least a subset of the moderately reiterated human histone genes in these cells. Quantitative and qualitative differences were also observed in the representation of histone mRNAs by Northern blot analysis using cloned human histone genes as hybridization probes. However, there was no apparent correlation between variations in the representation of transcripts from various copies of the histone genes, variations in histone gene organization, and the extent of tumor progression.
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PMID:Variations in the organization and expression of human histone genes in normal diploid and tumor cell lines. 620 Nov 32

Nuclear organizer regions (NORs) code for ribosomal RNA and are associated with non-histone nucleoproteins, which can be identified by silver staining (AgNORs). AgNORs have been correlated to proliferative activity of tumors and hence may be prognosis-related. The present study evaluates AgNOR counts in inflammatory lesions of the uterine cervix, cervical intra-epithelial neoplasia, and invasive cervical squamous carcinoma. Significant variation in AgNOR counts were observed between the three study groups, with invasive carcinoma showing maximum counts. Further, a highly significant positive correlation was observed between AgNOR counts and tumor progression. These results therefore suggest that AgNOR counts may be of significance in the evaluation of cervical carcinogenesis and could elaborate histopathological diagnosis of cervical lesions.
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PMID:Argyrophilic nucleolar organizer regions (AgNORs) in inflammatory pre-malignant and malignant lesions of the uterine cervix. 836 93

A point mutation in PKCalpha was originally discovered in a subpopulation of human pituitary tumors characterized by their invasive phenotype, and the same mutation was also seen in some thyroid neoplasms. To investigate the role of this mutation in tumorigenesis, normal and mutant human PKCalpha cDNAs were overexpressed in Rat6 embryo fibroblasts (R6). When extracts of R6 cells that expressed either the normal or mutant PKCalpha were assayed in the presence of calcium, phosphatidylserine and the phorbol ester TPA, for phosphorylation of either histone IIIS or the EGF-receptor peptide, both extracts gave similar results. However, the subcellular localization of the two proteins differed. Immunohistochemistry studies indicated that after treatment with TPA normal PKCalpha mainly translocated to the plasma membrane, but mutant PKCalpha translocated mainly to the perinuclear region and slightly to the nucleus. Furthermore, the cells that expressed the mutant PKCalpha displayed a decreased requirement for serum when compared to the cells expressing the normal human PKCalpha, and they formed small colonies in soft agar. By contrast, the cells expressing the normal human PKCalpha failed to form colonies in soft-agar. Thus, ectopic expression in rat fibroblasts of this mutant human PKCalpha sequence alters the growth properties of these cells and, when activated, the mutant PKCalpha displays aberrant intracellular translocation. Therefore, this mutation in PKCalpha could contribute to the process of tumor progression in certain human tumors.
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PMID:Ectopic expression of a mutant form of PKCalpha originally found in human tumors: aberrant subcellular translocation and effects on growth control. 903 75

Elevated levels of protein kinase C (PKC) are associated with increased metastatic capacity in both human breast cancer cells and breast tumors. MCF-7 breast cancer cells stably transfected with PKC-alpha were recently shown to display a more aggressive phenotype and increased tumorigenicity in nude mice. To identify genes involved in the progression to the aggressive phenotype, mRNA differential display was performed to isolate cDNAs that are differentially expressed between the parental, non-metastatic MCF-7 cell line and the metastatic derivative MCF-7-PKC-alpha cell line. One cDNA was identified which was upregulated and four cDNAs were downregulated in MCF-7-PKC-alpha cells. The upregulated cDNA may be a differentiation-specific gene as it is 100% homologous to a putative glialblastoma cell differentiation-related protein, GBDR1. DNA sequence analysis and flow cytometry revealed that three of the downregulated cDNAs correspond to histone 3.B, and integrins alpha3 and alpha6. The fourth downregulated cDNA clone, G2Q, is a novel sequence. G2Q is expressed in normal breast and bronchial tissue, but is downregulated in a variety of tumor cell lines and in aggressive primary and secondary breast tumors, suggesting that G2Q may be a useful prognostic indicator of tumor aggressiveness. Further, downregulation of G2Q expression in the non-metastatic MCF-7 cells by antisense oligonucleotides resulted in increased in vitro invasive capacity of these cells in a Matrigel matrice. This study provides the basis for identifying new genes involved in breast tumor progression and the role that PKC plays in the pathogenesis of this cancer.
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PMID:Isolation of protein kinase C-alpha-regulated cDNAs associated with breast tumor aggressiveness by differential mRNA display. 1020 Mar 47

In an attempt to elucidate the potential of premeiotic male germ cells to malignant transformation both the invasiveness and the differential gene expression of several putative tumor markers of the spermatogonia-derived cell line GC-1spg and the spermatocyte-derived cell line GC-4spc were analyzed. Studies, using RT-PCR analysis, of the expression pattern of the alkaline phosphatase isoenzymes which serve as markers for testicular germ cell tumors demonstrated that the expression of the endogenous mouse embryonic alkaline phosphatase (EAP) is upregulated in the GC-1spg cell line. Additionally, after transfection of GC-1spg cells and GC-4spc cells with a GCAP-CAT construct, an increased promoter activity of the human germ cell alkaline phosphatase (GCAP), the equivalent human isoenzyme of EAP, was shown in GC-1spg. Furthermore, an in vitro Matrigel invasion assay revealed a significant higher invasive potential of GC-1spg cells as compared to GC-4spc cells. Finally, a suppression subtractive hybridization on RNA of invasive GC-1spg cells and non-invasive GC-4spc cells was performed. In total, 31 cDNA sequences were isolated and further analyzed. Among these, 18 known sequences and 13 unknown sequences were determined. Northern blot analysis revealed that one unknown gene and eight known genes, namely integrin alpha 6, L6 antigen, annexin VIII, BVL-1 retrotransposon, protective protein, replacement variant histone 3.3, alpha-catenin and LPS-binding protein, are over-expressed in invasive GC-1spg cells. Taken together, both the enhanced invasive activity of GC-1spg cells and the upregulated expression of genes involved in the process of tumor progression suggest that the immortalized spermatogonia-derived cell line GC-1spg does have a higher potential to malignant transformation than the immortalized spermatocyte-derived cell line GC-4spc.
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PMID:Isolation and characterization of differentially expressed genes in invasive and non-invasive immortalized murine male germ cells in vitro. 1117 88

Low oxygen tension influences tumor progression by enhancing angiogenesis; and histone deacetylases (HDAC) are implicated in alteration of chromatin assembly and tumorigenesis. Here we show induction of HDAC under hypoxia and elucidate a role for HDAC in the regulation of hypoxia-induced angiogenesis. Overexpressed wild-type HDAC1 downregulated expression of p53 and von Hippel-Lindau tumor suppressor genes and stimulated angiogenesis of human endothelial cells. A specific HDAC inhibitor, trichostatin A (TSA), upregulated p53 and von Hippel-Lindau expression and downregulated hypoxia-inducible factor-1alpha and vascular endothelial growth factor. TSA also blocked angiogenesis in vitro and in vivo. TSA specifically inhibited hypoxia-induced angiogenesis in the Lewis lung carcinoma model. These results indicate that hypoxia enhances HDAC function and that HDAC is closely involved in angiogenesis through suppression of hypoxia-responsive tumor suppressor genes.
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PMID:Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. 1128 70

Differential acetylation of histones and transcription factors plays an important regulatory role in developmental processes, proliferation and differentiation. Aberrant acetylation or deacetylation leads to such diverse disorders as leukemia, epithelial cancers, fragile X syndrome and Rubinstein-Taybi syndrome. The various groups of histone acetyltransferases (CBP/p300, GNAT, MYST, nuclear receptor coactivators and TAFII250) and histone deacetylases are surveyed with regard to their possible or known involvement in cancer progression and human developmental disorders. Current treatment strategies are discussed, which are still mostly limited to histone deacetylase inhibitors such as trichostatin A and butyrate.
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PMID:Histone acetylation and disease. 1143 34

In recent years, significant progress has been made in understanding the nature of the human genome and the role that genes and their related proteins play in both normal and diseased cells. It has been proven that many cancers are caused by the mutation of certain genes or lack of gene function. The introduction of those genes into cancer cells where gene function is compromised, can work to restore gene function and stop tumor progression. There have been numerous clinical trials, which have shown that gene therapy products are efficacious in humans. The RIZ1 gene is a member of a superfamily of histone/protein methyltransferases. The gene is commonly inactivated in human cancers. Gene knock-out study has established RIZ1 as a tumor susceptibility gene in mice. The gene has potent tumor suppressive activities in causing apoptosis, G2/M arrest, or both. Preclinical animal studies have shown that a recombinant adenovirus expressing the gene, AdRIZ1, can suppress the growth of colon cancer xenografts. Therefore, AdRIZ1 shows promise as a new generation of gene therapy products to enter the clinic.
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PMID:The tumor suppressor gene RIZ in cancer gene therapy (review). 1174 55

Cancer/testis (CT) antigens are a category of tumor antigens with normal expression restricted to male germ cells in the testis but not in adult somatic tissues. In some cases, CT antigens are also expressed in ovary and in trophoblast. In malignancy, this gene regulation is disrupted, resulting in CT antigen expression in a proportion of tumors of various types. Since their initial identification by T-cell epitope cloning, the list of CT antigens has been greatly expanded through serological expression cloning (SEREX) and differential mRNA expression analysis, and approximately 20 CT antigens or antigen families have been identified to date. Characteristics commonly shared by CT antigens, aside from the highly tissue-restricted expression profile, include existence as multigene families, frequent mapping to chromosome X, heterogeneous protein expression in cancer, likely correlation with tumor progression, induction of expression by hypomethylation and/or histone acetylation, and immunogenicity in cancer patients. Spontaneous humoral and cell-mediated immune responses have been demonstrated against several CT antigens, including NY-ESO-1, MAGE-A, and SSX antigens. Since CT antigens are immunogenic and highly restricted to tumors, their discovery has led directly to the development of antigen-specific cancer vaccines, and clinical trials with MAGE-A and NY-ESO-1 are in progress.
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PMID:Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. 1244 78


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