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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conversion of choline in cultures of the human neuroblastoma cell lines, LA-N-1 and LA-N-2 cells, was investigated in order to identify potential precursors in acetylcholine (AcCho) synthesis. LA-N-1, a catecholaminergic and LA-N-2, a cholinergic, cell line were incubated with [3H-methyl]choline (Cho) for varying periods of time up to 72 h. The radioactivity present in lipids and water-soluble metabolites increased linearly up to 24 h in both cell lines. Approximately 20% of the radioactivity associated with the water-soluble metabolites in both control (untreated) and retinoic acid-induced differentiated (RA-treated cells) LA-N-2 cells was present as Cho and AcCho. There was no detectable AcCho in the catecholaminergic cell line, LA-N-1. The untreated and RA-treated LA-N-1 and LA-N-2 cells were labeled for 24 h with [3H-methyl]Cho, followed by a chase in growth medium containing 100 microM unlabeled choline. The distribution of radioactivity in the LA-N-2 cells was 6-10% of AcCho, 84-89% as phosphocholine (PCho), 1-3% as glycerophosphocholine (GroPCho), and 2-4% as Cho. The distribution of radioactivity in the LA-N-1 cells was similar except for the absence of AcCho. The distribution of radioactivity in the culture medium of LA-N-1 cells was 70-80% as Cho, 20-30% as PCho, and 1-3% as GroPCho. In contrast, the radioactivity was equally distributed between Cho (50%) and PCho (50%), with only 1-3% as GroPCho in the medium of LA-N-2 cells.
Mol Chem Neuropathol 1991 Feb
PMID:The metabolic fate of [3H-methyl]choline in cultured human neuroblastoma cell lines, LA-N-1 and LA-N-2. 191 Mar 57

We and others have previously reported that transforming growth factor-alpha (TGF alpha) expression is hormonally responsive and its expression is coregulated with that of its receptor [the epidermal growth factor (EGF) receptor]. The 5'-flanking region of the TGF alpha gene was characterized to determine whether it could confer hormone responsiveness to a reporter gene (luciferase) in human mammary carcinoma cells (MDA468). This segment of the gene is GC rich and contains an element strikingly similar to the core element of the EGF receptor gene that has been shown to mediate both basal and hormone-stimulated expression of the EGF receptor. We now report that a 313-basepair (bp) proximal element of the TGF alpha 5'-flanking region (-373 to -59 relative to the TGF alpha translation start codon) is capable of conferring responses to phorbol ester and EGF. This gene segment does not contain the EGF receptor gene homolog or potential AP-2-binding sites, suggesting that these elements are not necessary for basal and EGF- or phorbol ester-responsive TGF alpha gene expression. This 313-bp proximal element also confers proper transcriptional initiation to the chimeric TGF alpha-luciferase reporter construct, indicating it is the TGF alpha promoter. A 1.1-kilobase segment of the TGF alpha 5'-flanking region also confers retinoic acid, thyroid hormone, and glucocorticoid responsiveness despite the absence of recognizable steroid hormone receptor-binding sites. These hormones stimulate reporter expression 1.5- to 2-fold in a dose-dependent manner. Extension of the 5'-flanking region to -3500 results in marked suppression of reporter gene expression. These results indicate that the TGF alpha gene 5'-flanking sequence contains the elements responsible for hormonal responsiveness of this gene and that these elements are distinct from those that regulate the expression of the EGF receptor gene.
Mol Endocrinol 1991 Apr
PMID:Transcriptional regulation of the human transforming growth factor-alpha gene. 192 84

Many essential biological pathways, including cell growth, development, and metabolism, are regulated by thyroid hormones (THs). TH action is mediated by intracellular receptors that belong to a large family of ligand-dependent transcription factors, including the steroid hormone and retinoic acid receptors. So far it has been assumed that TH receptors (TRs) regulate gene transcription only through the classical protein-DNA interaction mechanism. Here we provide evidence for a regulatory pathway that allows cross-talk between TRs and the signal transduction pathway used by many growth factors, oncogenes, and tumor promoters. In transient transfection studies, we observed that the oncogenes c-jun and c-fos inhibit TR activities, while TRs inhibit induction of the c-fos promoter and repress AP-1 site-dependent gene activation. A truncated TR that lacks only 17 amino acids from the carboxy terminus can no longer antagonize AP-1 activity. The cross-regulation between TRs and the signal transduction pathway appears to be based on the ability of TRs to inhibit DNA binding of the transcription factor AP-1 in the presence of THs. The constituents of AP-1, c-Jun, and c-Fos, vice versa, can inhibit TR-induced gene activation in vivo, and c-Jun inhibits TR DNA binding in vitro. This novel regulatory pathway is likely to play a major role in growth control and differentiation by THs.
Mol Cell Biol 1991 Dec
PMID:Novel pathway for thyroid hormone receptor action through interaction with jun and fos oncogene activities. 194 74

The presence of the trivalent metallic cations, aluminum and boron, in the culture medium of differentiated human LAN-5 neuroblastoma cells results in increased amounts of specific isomers of microtubule-associated tau proteins. The cells were differentiated to a neuronal phenotype by the addition of retinoic acid. Six-day exposures of the differentiated cells to a 1-mM dose of aluminum or boron yielded increases in tau protein immunoreactivity to the monoclonal antibodies Tau-1 and Alz-50. Significant increases in immunoreactivity were seen at treatment levels of aluminum down to 100 microM. The increases in tau proteins were independent from increases in levels of total cell protein. Control cultures treated with the divalent cations zinc and iron showed no increases in levels of tau proteins.
Mol Chem Neuropathol 1991 Jun
PMID:Effects of aluminum on tau proteins in human neuroblastoma cells. 195 63

This study aims to elucidate gene expression of laminin and its role in expansion of the blastocyst during mouse early embryo-genesis. The gene expression of laminin, in particular the B1 subunit and the synthesis of laminin polypeptides, was examined during the expansion of blastocyst by a RNA-blot hybridization with 32P-labeled laminin B1 cDNA and immunoprecipitation followed by a SDS-PAGE, respectively. Laminin B1 transcript was actively expressed in the blastocyst stage of embryos. The gene expression of laminin B1 and the synthesis of laminin protein were also increased when blastocyst was expanded. Treatments of cAMP analogue, isobutylmethylxanthine, forskolin, and cholera toxin, which are known to stimulate the blastocyst expansion, increased laminin B1 transcript levels and synthesis of laminin polypeptides. Treatment with retinoic acid, a known regulator of laminin gene expression, not only increased the gene expression of laminin but stimulated the blastocoel expansion without a significant increase in intracellular cAMP levels. These results indicate that laminin gene expression may play an important role in the process of blastocyst expansion in the mouse preimplantation embryos.
Mol Reprod Dev 1990 Nov
PMID:Regulation of laminin gene expression in the expansion of mouse blastocysts. 196 57

Retinoic acid (RA) induces terminal granulocytic differentiation of the HL-60 promyelocytic leukemia cell line as well as certain other human myeloid leukemias. Specific RA receptors that are members of the steroid-thyroid hormone superfamily of nuclear transcription factors have recently been identified. We developed an HL-60 subclone that was relatively resistant to RA-induced differentiation. Specific nuclear RA receptors in this RA-resistant subclone had a decreased affinity for RA and exhibited a lower molecular weight compared with nuclear RA receptors from the RA-sensitive parental HL-60 cells. Retroviral vector-mediated transduction of a single copy of the RA receptor (RAR-alpha) into this RA-resistant HL-60 subclone restored the sensitivity of these cells to RA. These observations indicate that RAR-alpha plays a critical and central role in mediating RA-induced terminal differentiation of HL-60 leukemia cells.
Mol Cell Biol 1990 May
PMID:Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-alpha). 2708 49

The clonal rat rhabdomyosarcoma cell line BA-HAN-1C is composed of proliferating mononuclear cells, some of which spontaneously fuse to terminally differentiated myotube-like giant cells. Both the induction of differentiation by retinoic acid (RA) and by sodium butyrate (NaBut), as well as the inhibition of proliferation by fetal calf serum (FCS)-depleted medium uniformly resulted in the same effects. There was a significant (p less than 0.001) inhibition of proliferation and induction of cellular differentiation, as evidenced by a significant (p less than 0.05) increase in creatine kinase activity. Furthermore, after exposure to RA-supplemented or FCS-depleted medium, a significant (p less than 0.001) increase in the number of myotube-like giant cells was observed. These effects were preceded by a uniform enhancement of c-raf mRNA expression, which became evident 6 h after exposure to RA, NaBut and FCS-depleted media. C-raf mRNA expression persisted at an elevated level throughout the observation period of 5 days after exposure to RA or NaBut, whereas the increased expression of c-raf mRNA observed after FCS-depletion declined near to the basal level after only 24 h. Furthermore, a transient c-fos mRNA expression was observed 15 and 30 min after exposure to RA-supplemented and FCS-depleted medium but not after exposure to NaBut. The present results suggest a possible role of c-raf in the regulation of differentiation and proliferation of this cell line. Since all our experiments with RA, NaBut and FCS-depletion resulted in an early peak of c-raf mRNA expression, it is suggested that this early peak may be sufficient to trigger events crucial for differentiation and proliferation of BA-HAN-1C tumor cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:Uniform response of c-raf expression to differentiation induction and inhibition of proliferation in a rat rhabdomyosarcoma cell line. 198 May 57

The relationship between terminal cell differentiation and changes in the subcellular levels of the HER-2/neu antigen was investigated in cultured human breast cancer cells: AU-565 cells (which overexpress the HER-2/neu gene) and MCF-7 cells (which do not overexpress this gene). Differentiation was achieved by treating the cells with mycophenolic acid (MPA), phorbol 12-myristate 13-acetate (PMA), retinoic acid (RA), or the TA-1 monoclonal antibody to the extracellular domain of the HER-2/neu protein. Ten to twenty percent of the cells in untreated, sparsely growing AU-565 cultures exhibited morphological maturation characterized by large lacy nuclei surrounded by sizable flat cytoplasms. A fraction of these cells harbored milk factors such as casein and large lipid droplets. Treatment of the AU-565 cells for 4 d with 9 microM MPA, 1.6 nM PMA, 2.5 microM RA, or 1 microgram/mL TA-1 antibody resulted in cell growth inhibition and an increase in the percentage of cells (48-97%) that exhibit a mature phenotype. MCF-7 cells were also susceptible to differentiation by MPA and RA, but to a lesser degree than the AU-565 cells. Differentiation in the AU-565 and MCF-7 cells was associated with reduced immunostaining for the HER-2/neu protein at the cell surface membrane and with a transient increased diffuse immunostaining for this protein in the cytoplasm.
Mol Carcinog 1990
PMID:Differentiation of cultured human breast cancer cells (AU-565 and MCF-7) associated with loss of cell surface HER-2/neu antigen. 198 May 88

Retinoic acid regulation of one member of the human class I alcohol dehydrogenase (ADH) gene family was demonstrated, suggesting that the retinol dehydrogenase function of ADH may play a regulatory role in the biosynthetic pathway for retinoic acid. Promoter activity of human ADH3, but not ADH1 or ADH2, was shown to be activated by retinoic acid in transient transfection assays of Hep3B human hepatoma cells. Deletion mapping experiments identified a region in the ADH3 promoter located between -328 and -272 bp which confers retinoic acid activation. This region was also demonstrated to confer retinoic acid responsiveness on the ADH1 and ADH2 genes in heterologous promoter fusions. Within a 34-bp stretch, the ADH3 retinoic acid response element (RARE) contains two TGACC motifs and one TGAAC motif, both of which exist in RAREs controlling other genes. A block mutation of the TGACC sequence located at -289 to -285 bp eliminated the retinoic acid response. As assayed by gel shift DNA binding studies, the RARE region (-328 to -272 bp) of ADH3 bound the human retinoic acid receptor beta (RAR beta) and was competed for by DNA containing a RARE present in the gene encoding RAR beta. Since ADH catalyzes the conversion of retinol to retinal, which can be further converted to retinoic acid by aldehyde dehydrogenase, these results suggest that retinoic acid activation of ADH3 constitutes a positive feedback loop regulating retinoic acid synthesis.
Mol Cell Biol 1991 Mar
PMID:Retinoic acid response element in the human alcohol dehydrogenase gene ADH3: implications for regulation of retinoic acid synthesis. 199 13

A cloned thymosin beta-10 cDNA was used to study modulation of thymosin beta-10 mRNA levels in the rat B104 neuroblastoma cell line in response to retinoic acid. Northern blot analysis revealed the presence of a single greater than 600-nucleotide thymosin beta-10 mRNA species that was constitutively expressed in proliferating neuroblastoma cells. Addition of retinoic acid to the culture medium induced a dose- and time-dependent increase in thymosin beta-10 mRNA abundance. Additional studies showed that although thymosin beta-4 and beta-10 are coexpressed in this cell line, the stimulatory action of retinoic acid is specific for the thymosin beta-10 gene. Serum was found to augment the stimulatory action of retinoic acid. Blockade of protein synthesis with cycloheximide abrogated the stimulatory action of retinoic acid upon thymosin beta-10 mRNA accumulation; this observation suggests that activation of the thymosin beta-10 gene in this cell line by retinoic acid is dependent upon the de novo synthesis of a labile protein. Collectively, these findings demonstrate that the developmentally regulated thymosin beta-10 gene is a target for morphogenic retinoids in cells derived from the neural crest.
J Mol Neurosci 1991
PMID:Retinoic acid and serum modulation of thymosin beta-10 gene expression in rat neuroblastoma cells. 205 65


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