UMLS:C0684249 - FACTA Search

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Query: UMLS:C0684249 (lung carcinoma)
23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible role of cyclic AMP (cAMP) in the regulation of the vasopressin (VP) gene was tested in two cellular expression systems: one cell line with endogenous VP expression and the other which was transiently with a VP promoter-luciferase fusion gene. 8,Bromo-cAMP stimulated the VP mRNA content about 4-fold in the human VP-expressing small cell lung carcinoma cell line GLC-8. The luciferase activity in P19 embryonal carcinoma cells which were transiently transfected with -174 to +44 of the 5'-flanking region of the human VP gene linked to the firefly luciferase gene, was stimulated about 2-fold by the cAMP analogue. The results indicate that cAMP plays a role in the upregulation of the VP gene and hence point to several putative nucleotide motives in the promoter functionally conferring this response.
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PMID:Vasopressin gene expression is stimulated by cyclic AMP in homologous and heterologous expression systems. 217 21

The gene encoding firefly luciferase has been used as a reporter gene for the study of gene function. The luciferase catalyzes its substrate and subsequently produces luminescence. In addition, it is not present in mammalian cells. We have therefore explored its use in monitoring the growth of tumors in vivo. The luciferase gene was transfected into two murine tumor lines, i.e. c162 melanoma and M109 lung carcinoma, and the luciferase activity associated with the cells was determined by a rapid chemiluminescent reaction. Luciferase activity was well-correlated with the number of tumor cells in vitro. Luciferase activity also correlated with the tumor burden in vivo, as well as with the effect of an adoptive T cell transfer therapy in the syngeneic C3H/HeN mice experimental tumor model. This assay offers the advantage of being quantitative, rapid, and reliable for the detection of tumor burden and for the evaluation of the effect of antineoplastic therapy.
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PMID:Luciferase activity as a marker of tumor burden and as an indicator of tumor response to antineoplastic therapy in vivo. 830 31

DMS-79 is a human cell line derived from a small cell lung carcinoma (SCLC), which expresses the pro-opiomelanocortin (POMC) gene. We took it as a model in which to study the mechanism of POMC gene expression in these tumors: precursor processing is altered and gene expression is essentially unresponsive to glucocorticoids. POMC gene structure appeared normal by Southern blot analysis, indicating that gene rearrangement was not responsible for its expression in DMS-79. Indeed, using transient expression of human POMC-luciferase fusion genes in DMS-79, we showed that (1) the normal human POMC promoter was functional in DMS-79, and (2) the same proximal promoter region (-417; + 21) produced the full transcriptional activity in DMS-79 and in the mouse pituitary cell line AtT-20. Progressive 5' deletion analysis revealed differences between AtT-20 and DMS-79: region (-611; -376) was active in AtT-20 and not in DMS-79, whereas region (-95; -161) was active in both cell lines and (-376; -417) was only active in DMS-79. The latter partially overlaps a motif homologous to the DE-2 rat element which confers the tissue-specific expression of POMC in AtT-20 cells; however, this motif had no effect in DMS-79. These data suggest that POMC gene transcription is achieved through a different set of transacting factors in DMS-79 and AtT-20. Altogether, our results provide evidence that DMS-79 is a valid model of tumors responsible for the ectopic ACTH syndrome and that the mechanism of POMC gene expression in these SCLC cells is different from that in pituitary cells.
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PMID:Functional analysis of the human pro-opiomelanocortin promoter in the small cell lung carcinoma cell line DMS-79. 880 Jun 43

Arginine vasopression (AVP) is synthesized in the magnocellular neurons of the hypothalamus and stored in the posterior pituitary. It has been shown that hypothalamic AVP mRNA is increased during experimental stimulation of osmotic and non-osmotic stimulation of AVP release. The mechanisms underlying the stimulation of AVP biosynthesis in these conditions are not known. The present study was, therefore, performed to measure AVP release, AVP mRNA level, and AVP gene promoter activity during osmotic and non-osmotic stimulation of AVP secretion in the small cell lung carcinoma (SCLC) cells. AVP release was measured by radioimmunoassay, steady state levels of AVP mRNA by solution hybridization, and AVP gene promoter activity exhibited by a 1.5 kb 5'-flanking AVP gene fragment fused to a luciferase reporter after SCLC cells were subjected to osmotic or non-osmotic conditions. High media osmolality (330 mOsm) significantly increased AVP release (control (C) 1.42 +/- 0.27 vs. High Osm 3.67 +/- 0.39 pg/2 x 10(6) cells, N = 9, P < 0.002); AVP mRNA (C 173.6 +/- 16.8 vs. High Osm 280.1 +/- 19.4 pg/2 x 10(6) cells, N = 7, P < 0.001); and AVP gene promoter activity (C 1353 +/- 99 vs. High Osm 2026 +/- 134 L.U./10(-4) U beta-gal, N = 8, P < 0.001). Non-osmotic stimulators. 0.1 microM endothelin 3 (ET3), 1 microM angiotensin II (AII), and 10 microM acetylcholine (Ach) significantly increased AVP release; ET3 (C 1.78 +/- 0.20 vs. ET3 6.85 +/- 1.86 pg/2 x 10(6) cells, N = 8, P < 0.02); AII (C 1.29 +/- 0.38 vs. AII 27.80 +/- 7.09 pg/2 x 10(6) cells, N = 5, P < 0.05) and Ach (C 1.14 +/- 0.33 vs. Ach 2.68 +/- 0.58 pg/2 x x10(6) cells, N = 6, P < 0.05). However, only ET3 significantly increased AVP mRNA (C 166.6 +/- 19.6 vs. ET3 254.4 +/- 25.6 pg/p x 10(6) cells, N = 5, P < 0.05) and AVP promoter activity (C 1515 +/- 163 vs. ET3 2389 +/- 342 L.U./10(-4) U beta-gal, N = 6, P < 0.05). To localize the region of the AVP promoter that mediates the osmotic stimulation and the effect of ET3, 5' deletions of the AVP promoter fragments terminating at -532, -211, and -102, was assessed. Only the promoter activity of the 1.5 kb construct, but not the deletion constructs, was significantly increased by ET3 or high osmolality. These results suggest that modulation of AVP gene transcription is, at least in part, responsible for increased AVP synthesis and release in response to osmotic and non-osmotic stimulation, and that the region of 5' flanking sequence between -1500 and -532 contains the elements responsible for the effects.
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PMID:Osmotic and non-osmotic regulation of arginine vasopressin (AVP) release, mRNA, and promoter activity in small cell lung carcinoma (SCLC) cells. 896 Dec 55

The present study represents a continuation of previous works in which we observed that lung carcinomas co-expressing MDM2 protein and p53 mutants (mt p53) exhibited more aggressive behaviour. In the above studies, we suggested a 'gain of function' mechanism of mt p53 proteins based on the fact that the MDM2 gene possesses a p53-responsive element (MDM2-p53RE). In this study, to prove our hypothesis, we selected 12 cases from a series of 51 bronchogenic carcinomas. In these 12 cases, we examined the ability of the expressed mt p53 to bind the MDM2-p53RE and correlated the findings with MDM2 expression. Furthermore, we constructed four of these p53 mutants and studied their transactivation properties by co-transfecting them with a reporter plasmid carrying MDM2-p53RE in the p53 null non-small-cell lung carcinoma cell line (NSCLC) H1299. We observed mutant p53 protein DNA-binding activity, which depended on the nature and the position of the amino acid substitution. The fact that the cases with DNA-binding activity were accompanied with MDM2 protein isoforms' overexpression is indicative of a 'gain of function' phenotype. This hypothesis was enforced by the findings of the transfection experiments, which revealed that certain p53 mutants enhanced the expression of the luciferase reporter gene either directly or indirectly via a dominant positive effect on the wild-type p53. In conclusion, this work is one first attempt to examine if the deregulation of the p53/MDM2 autoregulatory feedback loop is due to novel properties of certain p53 mutants in the specific environment of a subset of bronchogenic carcinomas.
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PMID:Effects of p53 mutants derived from lung carcinomas on the p53-responsive element (p53RE) of the MDM2 gene. 947 31

Multiple transcripts derived from the gene encoding rat thyroid-specific enhancer-binding protein (T/EBP)/thyroid-specific transcription factor-1 (TTIF-1) were identified by complementary DNA cloning and sequencing, and Northern blotting analyses. Six different types of complementary DNAs were identified that differ at their 5' noncoding regions; four contain an intron of different lengths, whereas the other two possess no intron. Ribonuclease protection analyses revealed that multiple promoters are scattered throughout the upstream region, and the usage of these different promoters together with alternative splicing leads to a family of T/EBP messenger RNA (mRNA) species. A similar pattern of expression was also found in the human T/EBP gene expressed in a lung carcinoma cell line. Longer T/EBP mRNAs are more abundant in rat FRTL-5 thyroid cells maintained in the absence of TSH (-TSH) than in cells maintained in the presence of TSH (+TSH). Transfection analyses using the rat T/EBP gene DNA upstream of the ATG initiation codon connected to the luciferase reporter plasmid showed a similar relative activity profile between -TSH and +TSH culture conditions, suggesting that the abundance of longer mRNAs in -TSH conditions may not directly correlate with differences in promoter activities. Rather, TSH status might have a role in maintaining the physiological state of the cells. The upstream DNA of the rat and human T/EBP genes share a cluster of high and low sequence similarities, and both possess respectively 24 and 18 putative T/EBP-binding sites throughout. Cotransfection analyses of the T/EBP promoter-reporter constructs with a T/EBP expression vector into human HepG2 cells, which do not express T/EBP, suggested that autoregulation may be involved in controlling both rat and human T/EBP gene expression.
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PMID:Multiple transcripts encoded by the thyroid-specific enhancer-binding protein (T/EBP)/thyroid-specific transcription factor-1 (TTF-1) gene: evidence of autoregulation. 952 87

We investigated the effects of hypoxia (< 2.5% O2) on rat manganese superoxide dismutase (MnSOD) gene promoter-luciferase reporter constructs in transiently transfected lung epithelial cells (A549, L2, and E1A-T2) and fibroblasts (R9Ab). We cloned MnSOD promoter-luciferase reporter constructs (numbers refer to length in base pairs [bp] in the 5' direction from the transcription initiation site): 2,505, 1,064, 507, 405, and 289 into pGL2-Basic, a promoterless, firefly luciferase vector. Lung cells were transfected with MnSOD promoter-reporter constructs with or without thymidine kinase-driven Renilla luciferase (pRL-TK), and were exposed to air/5% CO2 or hypoxia (2.5% O2/5% CO2/balance N2) for 24 h. Hypoxia caused a significant (by two-way analysis of variance) consistent increase in luciferase in the A549 cell (human lung carcinoma) line. Greatest expression (> 3-fold increase) in hypoxia was associated with the 2,505-bp MnSOD promoter (normalized to cellular protein). Azide (10 microM) did not increase expression of the MnSOD reporter constructs. The 289-bp promoter was sufficient to express the reporter in air and to increase its expression in hypoxia. Promoter activity of the rat MnSOD 5' region, assessed by luciferase reporter constructs in A549 cells, increased in hypoxia. The increase was exclusive to A549 cells and did not occur in other cells.
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PMID:Hypoxic modulation of manganese superoxide dismutase promoter activity and gene expression in lung epithelial cells. 1038

Chromium(VI) regulation of gene expression has been attributed to the generation of reactive chromium and oxygen species, DNA damage, and alterations in mRNA stability. However, the effects of Cr(VI) on signal transduction leading to gene expression are not resolved. Therefore, this study investigated the effects of Cr(VI) on basal and tumor necrosis factor-alpha (TNF-alpha)-induced transcriptional competence of nuclear factor-kappaB (NF-kappaB) in A549 human lung carcinoma cells. Pretreatment of A549 cells with nontoxic levels of Cr(VI) inhibited TNF-alpha-stimulated expression of the endogenous gene for interleukin-8 and of an NF-kappaB-driven luciferase gene construct, but not expression of urokinase, a gene with a more complex promoter. Chromium did not inhibit TNF-alpha-stimulated IkappaBalpha degradation or translocation of NF-kappaB-binding proteins to the nucleus. However, Cr(VI) pretreatments prevented TNF-alpha-stimulated interactions between the p65 subunit of NF-kappaB and the transcriptional cofactor cAMP-responsive element-binding protein-binding protein (CBP). This inhibition was not the result of an effect of chromium on the protein kinase A catalytic activity required for p65/CBP interactions. In contrast, Cr(VI) caused concentration-dependent increases in c-Jun/CBP interactions. These data indicate that nontoxic levels of hexavalent chromium selectively inhibit NF-kappaB transcriptional competence by inhibiting interactions with coactivators of transcription rather than DNA binding.
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PMID:Chromium(VI) inhibits the transcriptional activity of nuclear factor-kappaB by decreasing the interaction of p65 with cAMP-responsive element-binding protein-binding protein. 1059 7

Transcriptional activation of human manganese superoxide dismutase (MnSOD) mRNA induced by a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), was examined to identify the responsive transcriptional regulator. The effect of various deletions and mutations within the 5'-flanking region of the human MnSOD gene promoter was evaluated using the luciferase reporter system in A549 human lung carcinoma cells. Deletion of a region between -1292 and -1202 nucleotides upstream of the transcription start site abolished TPA-responsive induction, whereas deletion of the putative binding sequence for NF-kappaB or AP-1 did not. The region between -1292 and -1202 contains a cAMP-responsive element-like sequence, TGACGTCT, which we identified as the manganese superoxide dismutase TPA-responsive element, MSTRE. Site-specific mutation of the MSTRE abolished the TPA-responsive induction, validating the critical role of this sequence. We detected specific MSTRE activity from nuclear extracts and demonstrated by antibody supershift assay that this activity is closely related to CREB-1/ATF-1. TPA treatment rapidly induced phosphorylation of the CREB-1/ATF-1-like factor via the protein kinase C pathway. These results led us to conclude that the human MnSOD gene having the promoter construct used in this study is induced by TPA via activation of a CREB-1/ATF-1-like factor and not via either NF-kappaB or AP-1. In addition, we found that this induction was blocked by inhibitors of flavoproteins and NADPH oxidases, indicating involvement of enhanced generation of superoxide radical anion as an upstream signal.
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PMID:Transcriptional activation of the human manganese superoxide dismutase gene mediated by tetradecanoylphorbol acetate. 1060 19

Adenoviral vectors are a widely used means of gene transfer. However, transgene expression after adenoviral administration varies among different carcinoma cell lines. We hypothesized that this variation is attributable, in part, to the presence of cell surface molecules involved in adenoviral infection. To test this, we first assessed adenovirus-mediated transgene expression in four human lung carcinoma cell lines and four human pancreatic carcinoma cell lines in terms of luciferase activities and found it to vary from 4.8 x 10(4) to 6.1 x 10(7) relative light units/microg of protein. Then, to determine whether the molecules involved in the entry of adenovirus into host cells were responsible for this variation, we evaluated the expression of alpha(v)beta5, alpha(v), beta3, alpha5, and beta1 integrins and that of coxsackievirus and adenovirus receptor (CAR) in these cell lines. Statistical analysis revealed that the levels of beta3 were associated with the levels of transgene expression. Blocking analysis showed that adenovirus-mediated gene transfer could be blocked by antibodies against these six molecules but not by the antibodies against alpha2 or alpha3 integrins, thus suggesting that the integrins alphavbeta5, alpha(v), beta3, alpha5, and beta1 and CAR molecules could limit adenovirus-mediated gene transfer when their levels fell below a certain threshold. Furthermore, cells expressing low levels of beta3 and resistant to conventional adenoviral vectors were susceptible to a vector containing the heparin-binding domain in its fiber, thus suggesting that redirecting vectors to receptors other than CAR may bypass the integrin pathway. These findings may have implications for improving the efficiency of adenovirus-mediated gene transfer and developing novel adenoviral vectors.
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PMID:Factors limiting adenovirus-mediated gene transfer into human lung and pancreatic cancer cell lines. 1063 62

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