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

The chromosomal constitution of a mammosomatotrophic and an inactive transplantable pituitary tumor induced in rats by 2,4,6-trimethylaniline was studied by the Giemsa-banding techniques. The inactive tumor line 7315i evolved from the active tumor line 7315a in one of the early transfers. A comparison was also made with chromosomal patterns of a transplantable rat hepatoma (7316A) induced by the same chemical carcinogen. Pituitary tumor line 7315a had a pseudotriploid complement with 63 chromosomes, whereas the inactive line 7315i was hypodiploid, with a dominant stemline of 36 chromosomes. The stemline chromosome number of the hepatoma was in the hypotetraploid region. Giemsa banding revealed that all chromosomes of the normal rat complement were present in both pituitary tumors. Four abnormal chromosomes were detected in the active tumor line and three in the inactive line. Both tumor lines contained a single minute chromosome. One common marker, a deleted chromosome No.1, was found in both pituitary tumors. This common marker chromosome was, however, not present in the hepatoma. The stemline karyotype of the hepatoma contained seven different markers, but none of them was identical to the abnormal chromosomes of the pituitary neoplasms. The findings suggested that the abnormal karyotypes of lines 7315a and 7315i could reflect the multisecretory activities of these neoplastic pituitary cells but that chromosomal localization of the secretory defect awaits exact genetic mapping of the rat chromosomes.
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PMID:Chromosome banding patterns of two transplantable pituitary tumors induced in rats by 2,4,6-trimethylaniline. 18 50

1. A protein which binds retinol in vitro with high affinity and specificity was detected by sucrose gradient centrifugation or by gel filtration after preincubating rat tissue cytosols with all-trans-[3H]retinol. This protein sediments in the 2 S region of sucrose gradients. Molecular size determination by gel filtration indicates a molecular weight of 16 000. 2. Competition studies revealed that only all-trans-retinol, not retinal or retinoic acid, competes for binding. The binding of radioactive retinol is reversible. 3. This protein was detected in cytosols of rat liver, lung, spleen, brain, testis, ovaries, uterus and intestinal mucosa whereas heart or gastrocnemius muscle seem to lack this protein. 4. The cellular retinol binding protein was found in fetuses as early as day 12 of the gestation period and possessed the same specificity for the ligand as the one in adult tissues. 5. This binding component was not detected in cytosols prepared from Novikoff hepatoma, ascites hepatoma AS-30D, mouse Ehrlich ascites tumor and mouse pituitary tumor cell line AtT 20. 6. The cellular retinol binding protein seems to be different from that described to be present in the serum as suggested by difference in size and by the inability of the antisera against the serum retinol binding protein to remove the cellular binding protein from the cytosol preparations.
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PMID:Cellular retinol-binding protein. 81 Jan 77

After transplantation of MtT/F4 pituitary tumor cells to male rats of the Fisher strain, the masculine type of hepatic steroid metabolism was changed into a feminine pattern of enzyme activities. Liver metabolism of steroid hormones in female rats was relatively unaffected following transplantation of pituitary tumor cells. Futhermore, extract from MtT/F4 tumors and "autonomous" pituitary tissue increased the 5alpha-reductase activity of hepatoma cells in the culture (HTC cells) at subsaturation concentrations of the substrate 4-androstene-3, 17-dione by decreasing the apparent Km of the enzyme. It is concluded that the pituitary tumor (in accord with the secretion from an "autonomous" pituitary gland) secretes "feminotropin," a novel hypophyseal principle that probably is an important regulator of hepatic steriod metabolism. It is suggested that pituitary tumor tissue of the MtT/F4 type could be used as source of feminotropin in purification studies.
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PMID:Feminization of hepatic S metabolism in male rats with a transplanted (MtT/F4). 94 49

The complete nucleotide sequence of a rat genomic DNA fragment of 6.9 kbp containing the entire N-myc gene was determined. A unique structural feature of the rat N-myc gene is the presence of two polyadenylation signals in the exon 3 region resulting in formation of two poly(A)+ N-myc mRNAs of 2.9 and 2.2 kb length. Elevated expression of the 2.9 kb mRNA, which was not due to gene amplification, was observed in normal rat tissues such as brain, adrenal and testis, and in rat tumor cells such as ascites hepatoma AH130, AH70Btc and AH7974 cells, and pituitary tumor GH3 cells. In contrast, expression of 2.2 kb mRNA, for which transcription was terminated at the upstream polyadenylation site, was observed only in GH3 cells.
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PMID:Different usage of two polyadenylylation signals in transcription of the N-myc gene in rat tumor cells. 171 66

We previously identified a naturally occurring peptide fragment derived from the carboxyl terminal region of the E-domain of pro-insulin-like growth factor II (proIGF-II117-156) in medium conditioned by cultured BRL-3A rat liver cells. In the present study we utilized a radioimmunoassay (RIA) for this peptide to measure physiological concentrations of the peptide in media and serum. Serum levels of the E-domain peptide were very high in the 5-day neonatal rat and declined thereafter to reach low levels in adult rat serum. Chromatography of adult rat serum on Sephadex G-75 in 1 M acetic acid yielded a single broad peak of E-peptide immunoreactivity that coeluted with a synthetic E-peptide standard. However, chromatography of day 5 neonatal rat serum on Sephadex G-75 yielded two peaks of immunoreactivity. One of the peaks coeluted with a synthetic E-peptide standard, whereas the other peak eluted in a region where higher molecular weight proteins typically elute. Experiments aimed at determining whether adult rat serum contained a binding protein for the E-domain peptide revealed that: (1) serum contains little, if any, binding protein for the E-domain peptide, (2) serum contains a proteinase activity that degrades the E-domain peptide, and (3) the proteinase activity can be eliminated by acetic acid/ethanol extraction. Of several rat cell lines tested (BRL-3A, rat embryo fibroblasts (REF), hepatoma cell lines (H4, HTC), GH3 pituitary tumor cells, and normal rat kidney fibroblasts (NRK], only BRL-3A and REF cells secreted measurable E-domain peptide into the medium. In addition, it was found that some component(s) of serum could stimulate secretion of E-domain peptide from BRL-3A and REF cells. Chromatography of the immunoreactivity from BRL-3A and REF-conditioned media on Sephadex G-75 in 1 M acetic acid yielded a single peak that coeluted with a synthetic E-domain peptide standard. Since secretion of the E-domain peptide parallels the expression of IGF-II, the RIA for the proIGF-II E-domain peptide may be useful for studies of the biosynthesis and secretion of IGF-II under different physiological conditions. The RIA for the IGF-II E-domain peptide has two technical advantages over the RIA for IGF-II, namely, the lack of interference by IGF binding proteins and the relative ease with which large quantities of pure antigen can be synthesized.
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PMID:The E-domain peptide of rat pro-insulin-like growth factor II (proIGF-II): properties of the peptide in serum and production by rat cell lines. 229 41

The purpose of this work was to study the effect of alpha-fetoprotein (AFP) over cell multiplication and the induction of an estradiol-17 beta (E2)-dependent marker, i.e., progestophilins in E-sensitive cells C2(9)RAP derived from a W/Fu rat pituitary tumor. These cells proliferate in isogeneic hosts under the influence of E2, while they proliferate in culture regardless of the presence of E2. C2(9)RAP cells were grown in medium supplemented with 10% horse serum. Progestophilin levels were measured 48 h after adding serum (20% horse, or castrated rat, or AFP-secreting tumor-bearing rat) and estrogen to the 10% horse serum-supplemented medium in which the cells were growing. Maximal induction of progestophilins was obtained at 3 X 10(-10) M E2 in cells grown in medium containing horse or castrated rat serum. In contrast, maximal induction of progestophilins required 3 X 10(-8) M E2 in cells grown in medium supplemented with the serum of Morris hepatoma 7777-bearing rats. This serum contained AFP levels comparable to those present at birth in the rat. 11-Methoxy-17 beta ethynylestradiol (R2858), a synthetic estrogen with little affinity for AFP, was also tested for its ability to induce progestophilins. The degree of maximal induction of progestophilins expressed as percentage of the respective control, was similar for all experimental groups, both with E2 and with R2858. In addition, we compared the free E2 levels in the culture medium with the progestophilin levels and the cell proliferation rate. We found that the progestophilin levels were maximal at free E2 concentrations above 11 pg E2/ml, whereas there was no correlation between the free E2 levels and the proliferation rate. Moreover, the proliferation rate of cells in medium supplemented with horse or castrated rat serum was maximal at concentrations of free E2 below 0.4 pg/ml; whereas cell proliferation was inhibited with hepatoma serum even at concentrations of free E2 of 44 pg/ml. We conclude that the effect of hepatoma serum on the E2 induction of progestophilins seems to be mediated by the effect of AFP on the availability of free estrogen, since it is abolished by the addition of both natural and synthetic estrogens. The inhibitory effect of hepatoma serum upon cell proliferation is not reversed by estrogens and thus seems to be mediated by mechanisms other than E2 trapping by AFP.
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PMID:Estrogen induction of progestophilins in rat estrogen-sensitive cells grown in media supplemented with sera from castrated rats and from rats bearing an alpha-fetoprotein-secreting hepatoma. 619 94

The role of DNA methylation in the expression of the rat growth hormone (rGH) gene was assessed by using a hypomethylating agent, 5-azacytidine, and the iso-schizomeric restriction enzymes MspI and HpaII. 5-Azacytidine increased rGH mRNA 3-8-fold in GH3D6 cells, a subclone of rat pituitary tumor cell lines that expresses one-tenth to one-fifteenth the GH expressed by two other clones, GH3 and GC. The effect was also detected at the level of pre-mRNA. The effect was independent of glucocorticoids and thyroid hormones and was found to be inheritable. The DNA methylation pattern generated by the isoschizomeric restriction enzymes indicated that the HpaII sites in the rGH gene were mostly methylated in GH3D6 cells but mostly unmethylated in GC cells. After treatment with 5-azacytidine, about 22% of these HpaII sites in GH3D6 cells became unmethylated. Thus, DNA methylation correlates inversely with the expression of the rGH gene in these cell lines. However, three other observations indicate that factors in addition to DNA methylation control rGH expression. First, in GC cells, even though most of the HpaII sites are unmethylated, the gene is not fully expressed. Second, in rat hepatoma cells, which do not express GH at all, the GH gene is less methylated than that in GH3D6 cells. Third, within the sensitivities of the assay methods, 5-azacytidine has no effect on the GH gene when it is completely silent. Taken together, the findings indicate that DNA methylation modulates but does not control GH gene expression. It is tempting to speculate that DNA methylation can influence expression only when the gene is committed to express.
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PMID:The effects of 5-azacytidine on the expression of the rat growth hormone gene. Methylation modulates but does not control growth hormone gene activity. 620 70

The induction of stress proteins was examined in rat myoblast cultures by two-dimensional gel electrophoresis. Data obtained by this analysis led to the following observations. (a) Arsenate, which behaves as a phosphate analogue in cellular phosphate-transfer reactions, stresses cultured rat cells and induces the synthesis of a unique set of proteins. (b) Most of the proteins synthesized after the addition of arsenate are identical to proteins synthesized in rat myoblasts in response to heat shock or arsenite stress. (c) However, both arsenic salts induce the synthesis of two unique proteins not induced by heat shock. (d) Five 25-30-kdalton stress proteins of rat cells do not contain methionine residues. (e) A majority of the proteins synthesized in stressed myogenic cells are also induced by stress in other rat cells such as hepatoma cells, pituitary tumor cells, and fibroblasts. The 25-30-kdalton stress-related proteins identified in myogenic cells, on the other hand, are induced in fibroblasts but not hepatoma or pituitary cells.
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PMID:Arsenate induces stress proteins in cultured rat myoblasts. 683 62

Non-pituitary tumors that produce adrenocorticotropic hormone (ACTH) exhibit resistance to the normal feedback effects of glucocorticoids on proopiomelanocortin (POMC) gene expression. This glucocorticoid resistance is typically complete, although some tumors show only relative glucocorticoid resistance in the clinical setting. The molecular mechanisms responsible for these clinical pathophysiologic observations are unknown, but might include glucocorticoid receptor defects or aberrant expression of enzymes or transporters that exclude glucocorticoids from access to their intracellular receptors. We examined whether ACTH-producing non-pituitary tumor cells might express 11beta-hydroxysteroid dehydrogenase (11beta-HSD), the principal 'gatekeeper' enzyme known to metabolize glucocorticoids. 11Beta-HSD mRNA and enzyme activity were assessed in DMS-79 cells, a line derived from an ACTH-producing small cell lung cancer. RT-PCR studies showed expression of mRNA encoding 11beta-HSD2 but not 11beta-HSD1 in DMS-79 cells. Control human fibroblasts expressed predominantly 11beta-HSD1 but also had detectable 11beta-HSD2 mRNA, while HepG2 hepatoma cells also expressed only 11beta-HSD2 mRNA. Whole cell assays in DMS-79 cells revealed 11beta-HSD activity with a Km for cortisol of 26.1 +/- 9.0 nM and Vmax of 57.0 +/- 5.9 pmol/h/mg protein. HepG2 cells expressed a similar high affinity enzyme activity, while control fibroblasts expressed 11beta-HSD activity with a Km for cortisol of 652 nM. Conversion of cortisol to cortisone in DMS-79 cells was inhibited to 7% of baseline by addition of 10 microM glycyrrhetinic acid. Dexamethasone (20 nM) was converted to a single product in DMS-79 cells at a rate of 17.2 pmol/h/mg protein; this activity was also inhibited by glycyrrhetinic acid. We conclude that DMS-79 cells express 11beta-HSD2. While DMS-79 cells harbor additional defects in glucocorticoid signaling, these data suggest that expression of 11beta-HSD2 might contribute to the development of the glucocorticoid-resistant phenotype of some ACTH-producing tumors.
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PMID:Expression of 11beta-hydroxysteroid dehydrogenase type 2 in an ACTH-producing small cell lung cancer. 988 91

The thyromimetic compound SK&F L-94901 shows more potent thyromimetic activity in the liver than in the pituitary gland or heart when administered to rats. The mechanisms of liver-selectivity of SK&F L-94901 were examined using cultured rat hepatoma cells (dRLH-84) and rat pituitary tumor cells (GH3), both of which showed saturable cellular uptake of tri-iodothyronine (T(3)). When isolated nuclei with partial disruption of the outer nuclear membrane were used, SK&F L-94901 competed for [(125)I]T(3) binding to nuclear receptors almost equally in dRLH-84 and GH3 cells. SK&F L-94901 also did not discriminate thyroid hormone receptors (TR) alpha1 and beta1 in terms of binding affinity and activation of the thyroid hormone responsive element. In intact cells, however, SK&F L-94901 was a more potent inhibitor of nuclear [(125)I]T(3) binding in dRLH-84 cells than in GH3 cells at an early phase of the nuclear uptake process and after binding equilibrium. These data suggest that SK&F L-94901 is more effectively transported to nuclear TRs in hepatic cells than in pituitary cells and therefore shows liver-selective thyromimetic activity. In conclusion, SK&F L-94901 discriminates hepatic cells and pituitary cells at the nuclear transport process. The cellular transporters responsible for this discrimination were not evident.
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PMID:Mechanism of liver-selective thyromimetic activity of SK&F L-94901: evidence for the presence of a cell-type-specific nuclear iodothyronine transport process. 1081 Mar 3


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