Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six human colon tumor cell lines were analyzed for their constitutive levels of the c-myc protein. The nuclear proto-oncogene, c-myc, was detected as an expressed product in all of the human colon tumor cell lines analyzed. The poorly differentiated cell lines HCT116, RKO and C showed c-myc levels that averaged 2-fold greater than their well-differentiated counterparts, i.e., GEO, CBS and FET. When c-myc levels and responses to serum induction were analyzed in the presence of inducers of differentiation, i.e., dimethylformamide, retinoic acid, sodium butyrate and TGF-beta, distinct patterns of sensitivity and resistance emerged. Nuclear c-myc levels were reduced in all the colon cell phenotypes treated with dimethylformamide or sodium butyrate. Only the well-differentiated human colon tumor cell lines were responsive to transforming growth factor-beta. Only one of the human colon tumor cell lines (GEO) responded to retinoic acid. Increased levels of c-myc protein were found to correlate well with greater growth rates and with poor differentiation class. Similarly, a parallel sensitivity to down-regulation of c-myc levels and attenuation of c-myc induction curves for inducers of differentiation were observed in growth sensitive human colon tumor cell lines.
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PMID:Sensitivity of nuclear c-myc levels and induction to differentiation-inducing agents in human colon tumor cell lines. 154 Sep 46

Expression of the N-myc oncogene is an important determinant of tumor behavior in human neuroblastoma. To study the regulation of N-myc, we have subcloned fragments of the 5' flanking region of the human N-myc gene upstream of the chloramphenicol acetyl transferase (CAT) reporter gene, and assayed for promoter activity in transient transfections into neuroblastoma and other cell lines. Upstream sequences were found to possess promoter activity to within 121 bp of the major cap site (-121). Negative regulatory elements were identified in regions approximately 2 kb and 500 bp upstream from the major cap site, as well as 150-1000 bp downstream. Promoter constructs containing downstream elements from bp +150 to +1000 were active in N-myc-expressing neuroblastoma cell lines, but not in non-expressing Epstein-Barr virus (EBV)-transformed 729-6 B-cell or HeLa cell lines, while those lacking this element were active in all cell types tested. All tested constructs retaining promoter activity showed decreased activity in parallel with the down-regulation of endogenous N-myc in response to treatment of transfected cells with retinoic acid. These studies suggest that N-myc regulation may be controlled at different levels, and provide a basis for further characterization of N-myc regulation in neuroblastoma.
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PMID:Cell type-specific expression and negative regulation by retinoic acid of the human N-myc promoter in neuroblastoma cells. 156 67

Both bacterial and mammalian heat shock proteins (HSP) are recognized by some T cells, and hsp60 recognition has been implicated in rheumatoid arthritis. We have developed a model to study the induction of hsp60 in human monocytic cell lines. An anti-mycobacterial hsp65 mAb (ML30), cross-reacting with human hsp60 was used to screen 21 human tumor cell lines in Western blot analysis. All T cell and B cell lymphomas constitutively expressed hsp60 protein at moderate to high levels, while little or no hsp60 protein was detected in two monocytic leukemia lines. Moderate to high levels of hsp60 mRNA and protein could be induced in the THP-I monocytic leukemia cell line by heat shock, retinoic acid, interferon (IFN)-gamma or tumor necrosis factor (TNF)-alpha treatment, the highest levels obtained with a combination of IFN-gamma/TNF-alpha. This was also seen using two rabbit anti-hsp60 antisera directed against the N-terminal or C-terminal part of the human hsp60 protein. The determinants detected by the ML30 mAb or the two rabbit anti-hsp60 antisera were not cell surface expressed, as measured with immunofluorescence (FACS) analysis on control cultured or cytokine treated cell lines. This could be a useful model for studies related to the induction of hsp60 in human cells.
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PMID:Induction of human hsp60 expression in monocytic cell lines. 156 88

A neural origin of Ewing's sarcoma (ES) has often been suggested and we have demonstrated neurofilament protein expression in ES cells. However, only the 200-kD subunit has been revealed in all of the ES cells analyzed. The 160- and 68-kD subunits were always absent. For these reasons, we have attempted to induce neural differentiation in 3 ES cell lines with different types of inducers: tetradecanoylphorbol-13-acetate (TPA) retinoic acid and nerve growth factor. When the cell lines were cultured for 7 days with TPA (10(-9) M) or retinoic acid (10(-7) M), only the 68-kD neurofilament subunit was slightly induced. No inducation was obtained when nerve growth factor was used, even at a 21-day culture. These results are in agreement with the putative neural origin of ES and may indicate an abnormal expression of neurofilament proteins in this tumor.
Tumour Biol 1992
PMID:Abnormal expression of neurofilament proteins in Ewing's sarcoma cell cultures. 158 95

Influences of indomethacin, which has been known as an inhibitor of the production of prostaglandins, on the suppression of footpad reaction (FPR) of BALB/c mice against sheep red blood cells by the painting of 12-O-tetradecanoylphorbol 13-acetate (TPA, a typical tumor promoter) were studied. The temporary suppressive effect by the painting of TPA (8 nmol) was abrogated by the painting of indomethacin (7-70 nmol) 60 min before TPA treatments. The lasting suppressive effect by TPA treatment (8 nmol/d) for 7 d following the painting of 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol), which is a typical tumor initiator, also disappeared when indomethacin (7 nmol) was painted 30-90 min before each TPA treatment. Influences of some inhibitors of tumor promotion on the lasting suppressive effect of FPR by DMBA and TPA were also tested. Painting of 0.6 mumol of 1-phenyl-2-pyrazolidone, 8.2 nmol of salcophytol A, 17 nmol of retinoic acid, 5.6 mumol of 3(2)-tert-butyl-4-hydroxyanisol, and 3 mumol of quercetin 45 min before each TPA treatment decreased the suppressive effect on the footpad reaction.
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PMID:Abrogation of the suppressive effect of 12-O-tetradecanoylphorbol 13-acetate and 7,12-dimethylbenz[a]anthracene on footpad reaction of mice by indomethacin and some inhibitors of tumor promotion. 160 43

It is well documented that activated macrophages, but not nonactivated ones, kill tumor cells in vitro without damaging normal cells. We, however, have previously shown that embryo-derived teratocarcinoma cells (F9, P19, PCC4) are efficiently killed by nonactivated macrophages as well as by activated ones. Whereas other tumor cells are killed extracellularly by macrophages, we found that F9 teratocarcinoma cells are phagocytosed alive by macrophages and subsequently killed intracellularly by a process dependent on intact lysosomal function. Neither the H-2 antigens nor the mRNAs for the alpha-chain and beta 2-microglobulin are detectable in embryo-derived teratocarcinoma cells. An obvious explanation for this unique killing is that the nonactivated macrophages recognize and kill these cells due to their lack of class I MHC antigen expression, assuming that class I MHC gene products on the target cells switch off the cytolytic machinery of nonactivated macrophages. Our present findings demonstrate that there is no correlation between H-2 antigen expression on tumor cells and their susceptibility to killing by macrophages. Retinoic acid-differentiated F9 cells and P19 cells expressing H-2 antigen after exposure to MAF (IFN-gamma) were sensitive to the killing by nonactivated macrophages. Hybrids that arose from fusion of P19 teratocarcinoma cells with embryonal normal fibroblasts (C57BL/6), which displayed the morphology of embryonal carcinoma stem cells and expressed H-2 antigens, were also sensitive to the killing by nonactivated macrophages. On the other hand, the H-2-negative testicular 402AX teratocarcinoma cells and K1735P melanoma cells were both resistant to the killing by nonactivated macrophages. We concluded that the unique killing of embryo-derived teratocarcinoma cells by nonactivated murine macrophages is not related to a lack of H-2 antigen expression.
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PMID:The unique killing of embryo-derived teratocarcinoma cells by nonactivated murine macrophages is not due to a lack of H-2 antigen expression. 162 57

Antiproliferative effects of free retinoic acid (RA) and liposome-encapsulated RA (RAlp) were compared in a squamous carcinoma system using both monolayer cells and multicellular tumor spheroids (MTS), an in-vivo-like model with three-dimensional histological structure. Initial studies examined the effect of lipid composition on the efficiency of RA encapsulation and on the subsequent toxicity of RAlp to red blood cells. In 5-day growth assays for monolayer cells, RA and RAlp (1 microM-0.1 nM) produced similar growth inhibition. In 6-day growth assays for MTS, RAlp was shown to have increased effectiveness. Liposomal uptake by the squamous carcinoma cells was examined by culturing monolayers and MTS with fluorescence-tagged liposomes and examining them under fluorescence microscopy between days 1 and 6. Phagocytosed liposomes were present, but their low levels suggested that other mechanisms of drug delivery such as adsorption, fusion or direct lipid transfer probably occurred for RAlp. Histological examination of MTS showed that RA and RAlp produced similar alterations. In this squamous carcinoma system, liposomes are effective in delivering retinoic acid and in producing biological effects in monolayer cells and within the three-dimensional structure of MTS.
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PMID:Antiproliferative effects of free and liposome-encapsulated retinoic acid in a squamous carcinoma model: monolayer cells and multicellular tumor spheroids. 162 40

Interactive regulation of gene expression by retinoic acid (RA) and adenosine monophosphate (cAMP) in mammary tumor cells was explored using Shionogi mouse mammary carcinoma cells (SC115) as a model and urokinase-type plasminogen activator (uPA) as a target gene product. Twenty-four hour treatment of SC115 cells with 100 nM RA, 1 mM 8-bromo-cAMP (BrcAMP), and 100 nM RA + 1 mM BrcAMP resulted in extracellular uPA activity increases of 1.4-fold, sevenfold, and 20-fold, respectively. These effects were dose-dependent with regard to both interacting members. Similar responses were obtained if 1 nM cholera toxin or 10 microM forskolin was used instead of the cAMP analog. Retinoids lacking the carboxylic acid function were inactive. The changes in uPA activity were accompanied by similar changes in uPA antigen concentration, as seen via Western blot analysis, and uPA mRNA abundance, as seen via Northern blot analysis. Actinomycin D, an inhibitor of RNA synthesis, blocked uPA stimulation by BrcAMP, suggesting that mRNA levels were transcriptionally regulated. The effect of BrcAMP on extracellular uPA activity was first evident at 2 h and peaked at approximately 6 h; the effect of RA alone and the synergistic response to joint treatment, however, followed a slower time course, requiring at least 12 h for initial expression and increasing gradually with time up to at least 48 h. Priming with RA for 48 h followed by extensive washing of the cells resulted in a threefold enhancement of the stimulatory effect of BrcAMP on uPA. Experiments utilizing the casein/plasminogen overlay method for the detection of uPA secretion by increased rate of uPA secretion per cell rather than to an increased fraction of uPA-secreting cells. Initial investigation of the mechanism of RA potentiation of cAMP responsiveness showed that RA did not alter cellular cAMP levels or total cAMP-dependent protein kinase A activity. Finally, the tumor promoter phorbol myristate acetate, an activator of protein kinase C, also increased SC115 cell uPA activity and synergized with RA. This raised the possibility that the enhancement of cAMP responsiveness by RA was indirectly mediated via an effect on protein kinase C. Experiments with protein kinase C-depleted cells, however, showed that this was not the case. In conclusion, RA treatment of SC115 cells potentiates the effect of cAMP on uPA expression at the single cell level via a partially irreversible mechanism independent of protein kinase C. The molecular target of RA and whether SC115 cell differentiation underlies the effect of RA remain to be established.
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PMID:Retinoic acid priming potentiates the induction of urokinase-type plasminogen activator by cyclic adenosine monophosphate in mouse mammary carcinoma cells. 164 61

Retinoic acid and its analogs, retinoids, have been shown to be useful in the treatment of several types of tumors. Retinoids elicit their biological activities by binding to their specific nuclear receptors, denoted as RAR-alpha, beta and gamma. RAR's have been established to be retinoid-dependent transcription factors which belong to the steroid/thyroid nuclear receptor superfamily. Recently, retinoic acid has been reported to be extremely effective in the treatment of acute promyelocytic leukemia (APL) giving more than 70% complete remission efficiency. APL has been characterized by the specific chromosomal translocation, t(15;17). Analysis of the t(15;17) breaking point revealed that (i) either RAR-alpha on chromosome 17 or the gene named myl on chromosome 15 is abnormal in APL cells, and (ii) the abnormal fused protein myl/RAR-alpha is expressed, which is suspected to cause the APL. Thus, RAR-alpha gene may be now regarded as one of tumor suppressor genes.
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PMID:[Retinoids and acute promyelocytic leukemia]. 165 89

We report a higher frequency of loss of heterozygosity at loci on the short arm of chromosome 3 in human epidermoid lung tumors than in other non-small cell lung tumors. This observation together with the already known involvement of the retinoids in the development of epidermoid metaplasia and neoplasia, especially in lung tissue, prompted us to investigate by RNAase protection assays the status of expression of a gene that maps on chromosome band 3p24 and codes for the B receptor for retinoic acid (RARB). We show that expression of RARB is detectable in normal lung tissue and in most of the cell lines derived from lung tumors, including the five non-small cell lines that clearly had a non-epidermoid phenotype. Strikingly, however, only one of the five epidermoid-tumor-derived cell lines studied showed detectable expression of RARB. Of two lines derived from adenosquamous tumors, one had a clear epidermoid differentiation, and this line also did not express RARB. Taken together, our results strongly implicate RARB in the evolution of epidermoid lung tumors.
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PMID:Implication of RARB in epidermoid (Squamous) lung cancer. 166 5


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