Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncogene activation has been suggested to play some role in determining the hormone independency of tumors. In order to study the role of protein kinase C in mediating the inhibition of the glucocorticoid-dependent transcription from the Mouse Mammary Tumor Virus (MMTV)-Long Terminal Repeat induced by overexpressed activated ras oncogene, we studied the effects of protein kinase C activators [the tumor promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA)] and inhibitors [1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7)] on the dexamethasone (DEX)-mediated activation of a MMTV-Long Terminal Repeat-chloramphenicol acetyltransferase (pMMTV-CAT) chimeric reporter gene transiently transfected into NIH-3T3 cells and in Ha-ras-transformed fibroblasts (T24-NIH-3T3). TPA (30 ng/ml) together with DEX (0.1 microM) treatment of NIH-3T3 cells resulted in a significant decrease of CAT activity from pMMTV-CAT, compared to DEX treatment alone. The addition of H-7 (40 microM) was able to overcome the TPA-induced inhibition of DEX-dependent transcription from pMMTV-CAT. DEX-dependent expression of pMMTV-CAT was significantly reduced in T24-NIH-3T3 with respect to wild-type NIH-3T3 cells. Treatment of T24-NIH-3T3 cells with either H-7 or TPA significantly enhanced or decreased, respectively, the DEX-dependent expression of pMMTV-CAT. TPA and/or H-7 did not affect CAT activity from either pMMTV-CAT in the absence of DEX or from CAT gene under the control of the SV40 promoter. Similar glucocorticoid receptor sites and binding affinities were observed in T24-NIH-3T3 or TPA-treated NIH-3T3 cells compared to wild-type untreated cells. Our data suggest that activation of PKC is involved in the reduced transcriptional regulatory activity of glucocorticoid hormone induced by overexpressed Ha-ras oncogene in NIH-3T3 fibroblasts.
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PMID:Tumor-promoting phorbol ester and ras oncogene expression inhibit the glucocorticoid-dependent transcription from the mouse mammary tumor virus long terminal repeat. 255

Photodynamic therapy (PDT) generates reactive oxygen species which initiate the cytotoxic events of this tumor treatment. We demonstrate that PDT mediated oxidative stress induced a transient increase in the early response genes c-fos, c-jun, c-myc, and egr-1 in murine radiation-induced fibrosarcoma cells. Incubation of exponentially growing cells with porphyrin based photosensitizers in the dark also induced an increase in mRNA levels of early response genes. However, the xanthine photosensitizer, rose bengal, produced increased c-fos mRNA levels only following light treatment. Nuclear runoff experiments confirmed that the induction of c-fos mRNA is controlled in part at the level of transcription. Likewise, a chloramphenicol acetyltransferase reporter construct containing the major c-fos transcriptional response elements was inducible by porphyrin and PDT. Signal transduction pathways associated with PDT mediated c-fos activation were examined by treating cells with protein kinase inhibitors. Staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine inhibited PDT mediated c-fos activation while N-(2-guanidinoethyl)-5-isoquinoline-sulfonamide had no effect. In addition, quinacrine, which can inhibit phospholipase activity, blocked PDT induced c-fos mRNA expression. These results suggest that photosensitizer mediated oxidative stress acts through protein kinase-mediated signal transduction pathway(s) to activate early response genes.
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PMID:Photodynamic therapy mediated induction of early response genes. 811 27

We investigated the inhibitory effects of intracellular cyclic adenosine monophosphate (cAMP) levels in regulating class 3 aldehyde dehydrogenase (aldh3) gene expression using cultures of primary rat hepatocytes and transient transfection experiments with HepG2 cells. In addition to regulation by an Ah receptor-dependent mechanism, expression of many members of the Ah gene battery have been shown to be negatively regulated. As was seen for the cytochrome P450 (cyp1A1) gene, aldh3 is transcriptionally inducible by polycyclic aromatic hydrocarbons (PAH), and this induction involving function of the arylhydrocarbon (Ah) receptor is inhibited by the protein kinase C (PKC) inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine di-HCl (H7) and staurosporine. However, PAH induction of ALDH-3 activity, protein, and mRNA was potentiated 2-4-fold by addition of the protein kinase A (PKA) inhibitors, N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide di-HCl (H8) and N-(2-guanidinoethyl)-5-isoquinolinesulfonamide HCl (HA1004). These PKA inhibitors had no effect on the PAH induction of the cyp1A1. Protein kinase A activity of cultured hepatocytes was specifically inhibited by H8 and HA1004 in a concentration-dependent manner, but not by H7, and there was an inverse correlation observed between potentiation of PAH-induced aldh3 gene expression and inhibition of specific PKA activity by the PKA inhibitors. The cAMP analog dibutyryl cAMP, the adenylate cyclase activator forskolin, and the protein phosphatase 1 and 2A inhibitor okadaic acid all dramatically inhibited both PAH induction and H8 potentiation of PAH induction of aldh3 expression but had no effect on induction of cyp1A1 expression in cultured hepatocytes. Both basal and PAH-dependent expression of a chloramphenicol acetyltransferase expression plasmid containing approximately 3.5 kilobase pairs of the 5'-flanking region of aldh3 (pALDH3.5CAT) were enhanced 3-4-fold by the PKA inhibitor H8 but not by the PKC inhibitor H7 (>20 microM). cAMP analogs, activators of PKA activity, or protein phosphatase inhibitors diminished expression of the reporter gene in a manner identical to the native gene in cultured rat hepatocytes. Using deletion analysis of the pALDH3.5CAT construct, we demonstrated the existence of a negative regulatory region in the 5'-flanking region between -1057 and -991 base pairs which appears to be responsible for the cAMP-dependent regulation of this gene under both basal and PAH-induced conditions. At least two apparently independent mechanisms which involve protein phosphorylation regulate aldh3 expression. One involves function of the Ah receptor which requires PKC protein phosphorylation to positively regulate both aldh3 and cyp1A1 gene expression and the other a cAMP-responsive process which allows PKA activity to negatively regulate expression of aldh3 under either basal or inducible conditions.
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PMID:cAMP-dependent negative regulation of rat aldehyde dehydrogenase class 3 gene expression. 901 60