Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibition of the growth of hormone related human tumor cells in vitro by GnRH agonists and antagonists suggests a direct effect on cell growth and proliferation, and this effect may be achieved through its receptors present in tumor cells. However, the nature of the GnRH receptors present in these tumors is controversial. To determine the molecular characteristics of GnRH receptors in such tumors, we used the reverse transcriptase/polymerase chain reaction (RT/PCR) technique to clone these receptors. Primers were selected from the human pituitary GnRH receptor cDNA sequence to amplify the open reading frame and parts of its 5' and 3'-untranslated sequences. Nucleotide sequencing of the GnRH receptor cDNAs from a breast tumor cell line (MCF-7) and from an ovarian tumor showed identity with that of the human pituitary GnRH receptor which binds GnRH with high affinity. GnRH receptor mRNA was found to be expressed in human pituitary, breast, breast tumor, ovary, ovarian tumor, prostate, prostate tumor and in breast tumor cell lines (MCF-7 and MDA-MB 468) and prostate tumor cell lines (PC-3 and LNCaP). These findings demonstrate that a mRNA representing the pituitary form of the GnRH receptor (which shows high affinity binding with GnRH) is also expressed in certain normal tissues and in hormone related human tumors and tumor cell lines derived from them.
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PMID:The nucleotide sequences of human GnRH receptors in breast and ovarian tumors are identical with that found in pituitary. 753 32

Approximately one third of breast cancers grow independently of estrogen, lack detectable estrogen receptor (ER) protein, and rarely respond to hormonal treatment. Previous studies correlated the lack of ER gene expression in ER-negative breast tumor cells with hypermethylation of a CpG island in the 5' region of the ER gene. In order to determine whether demethylation of the ER gene in the ER-negative human breast cancer cell line MDA-MB-231 could affect ER transcription, cells were treated with two inhibitors of DNA methylation, 5-azacytidine or 5-aza-2'-deoxycytidine. DNA from cells treated with either drug became partially demethylated at several methylation-sensitive restriction enzyme sites, including HhaI, NotI, and SacII, within the ER CpG island. This demethylation correlated with reexpression of the ER gene as detected by reverse transcriptase-PCR and production of ER protein as detected by Western blot analysis. ER produced in drug-treated cells was functionally active as demonstrated by its ability to activate transcription of estrogen-responsive genes. These results suggest that DNA methylation of the ER CpG island may play a role in suppression of ER gene expression in ER-negative breast cancer cells.
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PMID:Demethylation of the estrogen receptor gene in estrogen receptor-negative breast cancer cells can reactivate estrogen receptor gene expression. 753

Wild-type as well as variant oestrogen receptor (ER) mRNAs with exon 5 and 7 deleted were identified in a panel of human breast tumour cell lines by reverse transcriptase-polymerase chain reaction followed by dideoxynucleotide sequence analysis, and then quantitated by ribonuclease protection analysis. All cell lines categorised as ER+ by ligand-binding analysis expressed both wild-type and variant ER transcripts. Most cell lines classified as ER- did not express any ER transcript. However, three ER- cell lines (BT-20, MDA-MB-330 and T47Dco) expressed both wild-type and variant transcripts. A differential pattern of expression of wild type to variant was seen in both ER+ and ER- cell lines, however this pattern was not paralleled by differences in ligand-binding activity. Breast tumour cell lines previously classified as ER- expressed significantly lower levels of ER transcripts than did their ER+ counterparts. In view of these findings, as well as earlier reports that the exon 5 deletion ER variant encodes a dominant-positive receptor, it seems clear that some cell lines are misclassified as ER-, and express both wild-type and variant ER mRNAs, and that the overexpression of this variant may account, in part, for their oestrogen-independent phenotype.
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PMID:Coexpression of wild-type and variant oestrogen receptor mRNAs in a panel of human breast cancer cell lines. 773 23

Competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase are currently used to treat patients with hypercholesterolaemia. These inhibitors affect not only cholesterol biosynthesis, but also the production of non-steroidal mevalonate derivatives, that are involved in a number of growth-regulatory processes. As a consequence, their potential use as anticancer drugs has been suggested. In order to examine long-term effects of this potential therapeutic approach, we cultivated the gastric carcinoma cell line, EPG85-257, and the breast tumour cell line, MDA-MB231, in the presence of increasing concentrations of the HMG-CoA reductase inhibitor, pravastatin. For both cell lines, this procedure led to the selection of resistant variants able to proliferate in more than 1000 microM inhibitor. By competitive reverse transcriptase/polymerase chain reaction assay (cRT-PCR), the expression of the mRNA for two key proteins of cellular cholesterol metabolism, HMG-CoA reductase and low-density lipoprotein (LDL) receptor, were analysed in sensitive and resistant cells. Despite similar growth rates, MDA-MB231 cells expressed approximately four times more HMG-CoA reductase mRNA than EPG85-257 cells and over 30 times more LDL receptor mRNA. Both mRNA species were coordinately regulated in the parental and in the pravastatin-resistant variant cells. Expression was highly stimulated (3- to 4-fold for the HMG-CoA reductase and 2- to 3-fold for the LDL receptor) in the resistant variants when cultured in lipoprotein-deficient medium in the presence of 1000 microM pravastatin. Immunocytological analysis of the expression of the HMG-CoA reductase and LDL receptor protein were in accordance with the data on specific mRNA expression obtained by cRT-PCR. Southern blot analysis revealed a 1.5-fold amplification of the HMG-CoA reductase gene in resistant MDA-MB231 cells, but not in the resistant EPG85-257 variant. Our data provide evidence for resistance mechanisms to pravastatin that are independent of the amplification of the HMG-CoA reductase gene. By analogy to the cell-culture models employed in this study, it is conceivable that similar mechanisms might occur in human tumour cells in vivo during long-term treatment with HMG-CoA reductase inhibitors. This might limit their application as chemotherapeutic anticancer agents.
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PMID:Effects of pravastatin, a hydroxymethylglutaryl-CoA reductase inhibitor, on two human tumour cell lines. 779 99

Using reverse transcriptase polymerase chain reaction amplification it was possible to detect the presence of oestrogen sulphatase mRNA in different hormone-dependent (MCF-7, T-47D) and hormone-independent (MDA-MB-231, MDA-MB-468) mammary cancer cell lines. The expression of this mRNA is significantly higher in T-47D and MDA-MB-231 than in the other cell lines, and a correlation of this expression with the enzymatic activities was observed. The progestagen Promegestone (R-5020) can significantly decrease the mRNA of the sulphatase in MCF-7 cells. As this progestagen can also inhibit the enzyme itself in the same mammary cancer cell line, it is suggested that for the decrease in the sulphatase activity not only the effect on the enzyme, but also the effect on transcriptional factor(s) which express this enzyme are involved. The present data not only contribute to the knowledge of the mechanism of the sulphatase activity, but also can open new possibilities in breast cancer treatment.
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PMID:Effect of the progestagen Promegestone (R-5020) on mRNA of the oestrone sulphatase in the MCF-7 human mammary cancer cells. 797 90

Oestradiol (E2) is one of the most important factors supporting the growth and evolution of breast cancer; consequently, to block this hormone has been one of the main targets in recent years. The evaluation of oestrogens (oestrone, oestradiol and their sulphates) in the breast tissue of post-menopausal patients with breast cancer indicates high levels, particularly of oestrone sulphate (E1S) which is 15-25 times higher than in the plasma. Two main pathways are involved in the formation of oestrogens the sulphatase pathway which transforms E1,S into oestrone (E1), and the aromatase pathway which converts androgens into oestrogens. Comparative studies in breast cancer tissues show that the sulphatase pathway is 50-300 times more important than that of the aromatase pathway. Using intact cells and physiological concentrations of E1S (5 x 10(9)M) the conversion to oestradiol was very intense with the hormone-dependent (T-171). MCF-7) breast cancer cells, but very little or no E2 was obtained with the hormone-independent (MDA-MB-231, MDA-MB-436) cells. However, when the latter cells were homogenized, the oestrone sulphatase became very intense. This contradiction in the comparison of the sulphatase activity of the intact cell and the homogenate of the hormone-independent cells can be explained by the presence of inhibitory factors or the absence of positive factor(s) involved in the enzyme activity, which could be related to the evolution of the cancer to hormone-independence. Testing different substances, it was proven that promegestone (R-5020), and danazol, as well as decapeptyl in the presence of heparin, are very active in inhibiting sulphatase activity in hormone-dependent breast cancer cells. Using reverse transcriptase-PCR it was possible to detect the presence of oestrone sulphatase mRNA in different mammary cancer cells. The expression of this mRNA is significantly higher in T-471) and MDA-MB-231 than in the other cell lines. A correlation of this mRNA with the enzymatic activities of oestrone sulphate was observed. The progestagen, R-5020, can significantly decrease the sulphatase mRNA in MCF-7 and T-471) cells. As this progestagen can also inhibit the enzyme itself, it is suggested that the decrease in sulphatase activity by antisulphatase agents in breast cancer cells is a complex mechanism involving not only the effect on the enzyme but also the transcriptional factor(s). It is concluded that in addition to the control of aromatase, specific inhibition of oestrone sulphatase with antisulphatase agents can open new possibilities in breast cancer treatment.
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PMID:Control and expression of oestrone sulphatase activities in human breast cancer. 894 93

In many cases of human cancer, the appearance of hypersialylated glycan structures is related to a precise stage of the disease; this may depend on altered regulation of one or more sialyltransferases genes. Since several distinct sialyltransferase enzymes arising from different unique genes transfer sialic acid residues in the same linkage onto the same acceptor, it is impossible to precisely determine which enzyme is involved in the observed phenotype based on enzymatic assays. We have developed a very sensitive and highly reproducible multiplex reverse transcriptase-polymerase chain reaction technique in order to monitor the expression of four human sialyltransferases genes ST6Gal I, ST3Gal I, ST3Gal III and ST3Gal IV in small cell samples. Multiplex PCR amplification using specific primers for each sialyltransferase and detection of amplification products by polyacrylamide gel electrophoresis is a method that is fast and easy to handle and has proven to be useful for establishing sialyltransferase patterns of expression in breast immortalized cell line HBL100 as well as in breast cancer cell lines MCF-7/6, MCF-7/AZ and MDA.
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PMID:Multiplex RT-PCR method for the analysis of the expression of human sialyltransferases: application to breast cancer cells. 953 Sep 53

Using reverse transcriptase-polymerase chain reaction amplification it was possible to detect the presence of type 1 human estrogen sulfotransferase (hEST1) mRNA in the hormone-dependent: MCF-7 and T-47D, and hormone-independent: MDA-MB-231 and MDA-MB-468, human breast cancer cells. The expression of this mRNA is significantly higher in the MDA-MB-468 cells and a correlation of this mRNA expression with the enzymatic activity was observed. The progestin promegestone (R-5020) at a low concentration (5 x 10(-7) M) can significantly increase the estrogen sulfotransferase activity and its mRNA in the hormone-dependent MCF-7 and T-47D cells. As estrogen sulfates are biologically inactive, the stimulatory effect on sulfotransferase by promegestone may open attractive possibilities in the control of estradiol in human breast cancer.
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PMID:Human estrogen sulfotransferase (hEST1) activities and its mRNA in various breast cancer cell lines. Effect of the progestin, promegestone (R-5020). 974 35

The most frequent site of breast cancer metastasis is bone suggesting that some breast cancers express proteins that facilitate this process. We evaluated whether a highly metastatic breast cancer cell line, MDA-MB-231, and a less metastatic breast cancer cell line, MCF-7, contain bone morphogenetic proteins (BMP). Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that MDA and MCF-7 cells contain mRNAs for BMP receptors IA, IB and II. RT-PCR indicated the presence of mRNAs for BMPs 2 and 3 but not 4 and 7 in breast cells. Using a RT-PCR strategy with molecular beacons, we found that the mRNA for BMP2 in MDA cells was decreased by 75% after a sublethal dose of radiation. An ELISA using an antibody specific for BMP2 demonstrated that BMP2 protein was reduced after radiation of MDA cells. The mRNA for BMP2 was expressed to a lesser extent in MCF-7 cells than MDA cells and was not altered after radiation treatment of MCF-7 cells as demonstrated by molecular beacon RT-PCR. Recombinant human BMP2 decreased the proliferation of MDA cells to a greater extent than MCF-7 cells. These results expand the number of tissues that contain BMPs and demonstrate the effect of this signalling pathway of the growth state of these tissues.
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PMID:Identification of bone morphogenetic proteins and their receptors in human breast cancer cell lines: importance of BMP2. 1062 28

The presence of an exon 1' sequence in the estrogen receptor alpha (ERalpha) mRNA was detected in different stocks of ER-positive MCF-7 human breast cancer cells by reverse transcriptase polymerase chain reaction (RT-PCR) and ribonuclease protection analysis (RPA), but not by Northern blot analysis. This mRNA, however, was not detectable in ERalpha-positive ZR-75-1 or ERalpha-negative MDA-MB-231 breast cancer cells, suggesting that exon 1' ER mRNA is differentially expressed in some but not all ER-positive cell lines, and then, only at very low levels.
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PMID:Differential expression of an estrogen receptor messenger RNA containing exon 1' sequences in MCF-7 breast cancer cell line stocks. 1068 May 97


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