Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relying heavily on studies of TAT regulation in cultured rat hepatoma cell lines, we have attempted in this brief review to discuss possible mechanisms for posttranscriptional regulation of glucocorticoid-sensitive enzymes and to chronicle the evidence for and against posttranscriptional mechanisms for specific enzyme induction by glucocorticoids. Initially, mechanisms were considered that would reconcile results showing sensitivity of both induction and deinduction of TAT to inhibitors of RNA synthesis with studies demonstrating first that glucocorticoids regulate the rates of specific enzyme synthesis and, then, that glucocorticoids regulate levels of enzyme-specific mRNA. Such reconciliation proved unnecessary when it was demonstrated that inhibitors of RNA synthesis such as actinomycin D were not specific for RNA synthesis, but also had effects on mRNA turnover and protein metabolism. The bulk of evidence to date establishes that glucocorticoids promote the production of enzyme-specific mRNA for the proteins whose synthesis is regulated by thses steroids. Nevertheless, there is still very little direct evidence that steroids can modulate rates of specific gene transcription. The glucocorticoid stimulation of mouse mammary tumor virus RNA production in cultured cell lines is the only example to date where such a mechanism is supported by RNA-DNA hybridization studies. Posttranscriptional actions of steroids on the turnover, processing, or extranuclear transport of specific mRNA precursors remain potential steps at which glucocorticoids might function. The rapid turnover of some glucocorticoid-regulated enzymes and their mRNAs not only ensures a rapid response to steroid addition or withdrawal, but also subjects these proteins to relatively large fluctuations upon alterations in overall protein or mRNA metabolism. Thus many of the inductions and repressions of hepatic TAT and TO by mediators other than the glucocorticoids may be attributable entirely to nonspecific mechanisms.
 ...
PMID:Posttranscriptional regulation of glucocorticoid-regulated functions. 4 Jan 16

Type-B mammary tumor virus particles were detected by electron microscopy in the submaxillary glands of 6 of 27 freshly trapped, pregnant wild mice (Mus musculus). Type-B particles were also detected in 3 9f 24 seminal vesicles and 2 pulmonary adenomas from wild mice. Intracytoplasmic type-A virus particles were found in 7 spontaneous nonmammary tumors (lymphoma, hepatoma, lung adenoma) of aging wild mice. Type-C virus particles were also detected in many of these tissues.
 ...
PMID:Mammary tumor virus particles in the submaxillary gland, seminal vesicle, and nonmammary tumors of wild mice. 16 6

Sialic acid content in breast or tumor tissue and serum of mouse strains that are either susceptible or resistant to breast cancer was measured at various age periods. Sialic acid content was also studied in normal lung tissue and in lung adenoma and hepatoma. Sialic acid levels during nonmalignant growth of a tissue were measured in breast tissue during pregnancy and lactation, and in regenerating liver, as well as in newborn and postnatal liver. The sialic acid content, when expressed per mg of protein, increased in mammary tumor, lung adenoma, and hepatoma. It also increased in nonmalignant growth of breast tissue during pregnancy and lactation and of regenerating liver and postnatal liver. Increase in sialic acid per mg DNA was observed only in lung tumors, regenerating liver, and postnatal liver. It appears that the changes in sialic acid level are independent of the normal or malignant growth of a tissue and that these changes might be the function of the parameter used to express the sialic acid values, i.e., either the DNA content or protein content of a given tissue.
 ...
PMID:Independence of sialic acid levels in normal and malignant growth. 16 79

A continuous line of buffalo rat hepatoma (HTC) cells has been successfully infected with mouse mammary tumor virus (MMTV) produced by the GR mammary tumor cell line. Uniform infection required initial exposure of the HTC cells to greater than 10(5) MMTV particles per cell. The resultant chronically infected cell population was found to have stably acquired 20-30 copies of MMTV DNA. The infected cells contain viral RNA and express viral antigens; however, very few MMTV particles are released into the culture medium. In spite of the biochemical evidence for infection, we have not detected any alterations in the morphology or growth properties of the infected HTC cells. As is the case in mammary tumor cells, the intracellular concentration of viral RNA is strongly stimulated (50-150 fold) by the synthetic glucorcorticoid, dexamethasone. Thus it appears that the mechanisms by which glucorticoids regulate MMTV gene expression in mouse cells are maintained when this virus infects nonmurine cells.
 ...
PMID:Infection of cultured rat hepatoma cells by mouse mammary tumor virus. 18 32

Mouse mammary tumor virus (MMTV) DNA in chronically infected rat hepatoma cells is maintained in both the integrated and unintegrated state. Fractionation of DNA by the procedure of Hirt (1967) as well as by sedimentation through alkaline sucrose suggests that about two thirds of the viral DNA is associated with high molecular weight cell DNA. The remainder of the viral DNA is unintegrated and is present primarily as linear or open circular duplexes consisting of a genome-length strand complementary to the viral RNA ("minus" strand) and "plus" strands of subgenomic length. Approximately 20% of the unintegrated MMTV DNA is present as double-stranded, covently closed circles (form I) with a molecular weight of 6 X 10(6) daltons. Form I viral DNA is found primarily in the nucleus, whereas the open forms are both nuclear and cytoplasmic.
 ...
PMID:Mouse mammary tumor virus DNA in infected rat cells: characterization of unintegrated forms. 18 33

Glucocorticoid hormones specifically increase the intracellular concentration of mouse mammary tumor virus (MMTV) RNA in a cultured cell line from a GR mouse mammary carcinoma (GR) and in an MMTV-infected rat hepatoma cell line (M1.19). In contrast, these steroids have no effect on the concentration of MMTV RNA in a lymphoma line, S49, from a Balb/c mouse. Using a molecular hybridization procedure to detect newly synthesized RNA, we have directly measured the effect of dexamethasone, a synthetic glucocorticoid, on the rate of MMTV RNA synthesis. In GR cells the hormone causes a 10-fold increase in the rate of synthesis of viral RNA without appreciably affecting the overall rate of cellular RNA synthesis. The transition from the basal to the maximally stimulated rate of MMTV RNA synthesis occurs within the earliest labeling period, 0-15 min after addition of the hormone. Thus, it appears that glucocorticoids regulate MMTV genes principally by this rapid and specific alteration of their rate of transcription. Similar results are obtained in M1.19 rat hepatoma cells. In contrast, dexamethasone does not affect the rate of viral RNA synthesis in S49 lymphoma cells.
 ...
PMID:Glucocorticoid-stimulated accumulation of mouse mammary tumor virus RNA: increased rate of synthesis of viral RNA. 19 23

Dexamethasone, a synthetic glucocorticoid, selectively increased the rate of synthesis of mouse mammary tumor virus (MTV) RNA in clonal isolates of chronically infected rat hepatoma tissue culture cells. This hormonal effect occurred extremely rapidly and appeared to be mediated directly by the glucocorticoid-specific receptor protein. In addition to the viral RNA, unintegrated MTV DNA was also detected in these cells. Several lines of evidence are consistent with the idea that the unintegrated viral DNA is synthesized by reverse transcription of MTV RNA. (i) Unintegrated viral DNA accumulated only in the presence of dexamethasone and was produced with a time course that closely paralleled the increased accumulation of viral RNA. (ii) Density labeling of the viral DNA revealed that both strands were newly synthesized, implying a non-semiconservative mode of replication. (iii) Inhibitors of viral RNA synthesis prevented the appearance of unintegrated viral DNA. These data suggest that the production of unintegrated MTV DNA after dexamethasone treatment occurs as a secondary consequence of the hormonal induction of synthesis of viral RNA. In contrast to infected rat hepatoma cells, no unintegrated MTV DNA was detected in mouse mammary tumor cells or mouse lymphoma cells, despite the presence of high levels of viral RNA.
 ...
PMID:Production of unintegrated mouse mammary tumor virus DNA in infected rat hepatoma cells is a secondary action of dexamethasone. 20 32

The production of mouse mammary tumor virus (MTV) is stimulated by treatment of mammary carcinoma cells with glucocorticoid hormones (e.g., dexamethasone). The reaction appears to be a primary and receptor-mediated phenomenon in which the rate of synthesis of MTV RNA is selectively increased; the maximally induced rate is reached within 15 min after addition of the hormone. Production of MTV RNA is also stimulated by dexamethasone in some but not all clonal isolates of nonmurine cells infected by the virus. Using restriction endonucleases, we have characterized both integrated and unintegrated viral DNA from clones of infected rat hepatoma (HTC) cells. We suggest that the site(s) in the rat cell genome into which MTV DNA integrates may be a determining factor for MTV RNA synthesis.
 ...
PMID:Mouse mammary tumor virus genes: regulation of expression by glucocorticoids and structural analysis with restriction endonucleases. 20 82

Rat hepatoma cells infected with mouse mammary tumor virus contain multiple forms of unintegrated viral DNA when grown in the presence of glucocorticoids. Using the DNA transfer procedure of Southern, we have prepared restriction endonuclease fragment maps of these forms of viral DNA. The maps indicate that: (i) the major species of viral DNA is a linear molecule of 5.9 X 10(6) Mr located in the cytoplasm; (ii) the nuclei contain covalently closed circular viral DNA of two distinct sizes (5.1 X 10(6) and 5.9 X 10(6) Mr) in addition to linear molecules (5.9 X 10(6) Mr); (iii) the linear molecule has specific termini; (iv) there is extensive homology between regions at or near termini of the linear molecule; (v) the predominant form of circular DNA lacks 1.2 kilobase pairs present in both the larger circular molecule and the linear molecule; and (vi) the sequences deleted from the majority of the circular DNA molecules are located at the ends of the linear DNA that are joined during circularization.
 ...
PMID:Mapping of linear and circular forms of mouse mammary tumor virus DNA with restriction endonucleases: evidence for a large specific deletion occurring at high frequency during circularization. 20 50

Rat hepatoma cells infected with mouse mammary tumor virus (MMTV) acquire viral DNA that becomes covalently linked to the cell DNA. Using restriction endonucleases and the DNA transfer procedure of Southern [Southern , E.M. (1975) J. Mol. Biol. 98, 503--517], we have studied the sites in cellular DNA into which MMTV DNA inserts. These experiments indicate that: (i) there are many sites in cell DNA into which MMTV DNA integrates; (ii) the junctions between viral and cellular DNA occur within a limited portion of the viral genome, (iii) clones that contain MMTV DNA do not necessarily produce viral RNA; and (iv) the extent of transcription and glucocorticoid responsiveness of MMTV proviruses may be dependent on the site(s) in cell DNA in which the viral DNA resides.
 ...
PMID:Integration and transcription of mouse mammary tumor virus DNA in rat hepatoma cells. 21 15


1 2 3 4 5 6 7 8 9 Next >>