Interaction of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 17 beta-estradiol in MCF-7 human breast cancer cells. 1993

M Moore, and T R Narasimhan, and X Wang, and V Krishnan, and S Safe, and H J Williams, and A I Scott
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 12-O-tetradecanoylphorbol-13-acetate (TPA) are both tumor promoters which act through different mechanisms. In MCF-7 human breast cancer cells, both TCDD and TPA inhibited constitutive and 17 beta-estradiol-induced cell proliferation but showed no apparent interactive effects. TCDD also inhibited the 17 beta-estradiol-induced secretion of the 52-kDa protein (procathepsin D) and induced CYP1A1 gene expression whereas TPA alone was inactive for these responses. Moreover, TPA did not modulate the TCDD-mediated antiestrogenic or induction responses and did not decrease levels of the nuclear Ah receptor complex as determined in a gel mobility shift assay using a 32P-dioxin responsive element (DRE). The interactions of TPA and TCDD on the metabolism of [13C]glucose to [13C]lactate was also investigated using 13C-nuclear magnetic resonance spectroscopy. The rate of formation of [13C]lactate from [13C]glucose in MCF-7 cells treated with DMSO (control), 1 nM 17 beta-estradiol, 1 nM TCDD, 1 nM TCDD plus 1 nM 17 beta-estradiol, and 0.1 ng/ml TPA plus 1 nM 17 beta-estradiol was 28, 48, 20, 22 and 50 fmol lactate formed/cell/h, respectively. Thus, TCDD, but not TPA, inhibited this estrogen-induced response. However, a comparison of the rate of lactate formation in cells treated with TCDD plus 17 beta-estradiol (22 fmol/cell/h) or TCDD plus 17 beta-estradiol plus TPA (61 fmol/cell/h) showed that TPA significantly inhibited the TCDD-mediated antiestrogenic response. The results of these studies in MCF-7 cells demonstrate that the interactions of TCDD and TPA are highly response-specific and do not involve TPA-mediated downregulation of the nuclear Ah receptor complex.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007773 Lactates Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D010088 Oxidoreductases The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9) Dehydrogenases,Oxidases,Oxidoreductase,Reductases,Dehydrogenase,Oxidase,Reductase
D011955 Receptors, Drug Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified. Drug Receptors,Drug Receptor,Receptor, Drug
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002402 Cathepsin D An intracellular proteinase found in a variety of tissue. It has specificity similar to but narrower than that of pepsin A. The enzyme is involved in catabolism of cartilage and connective tissue. EC 3.4.23.5. (Formerly EC 3.4.4.23).
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450

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