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Biomedical subjects

A Valette

Publications and source records attributed to A Valette.

At least 55 records · Page 3Linked to original sources
PubMed1990

Transforming growth factor beta 1 is a potent survival factor for rat embryo motoneurons in culture.

We have studied the effects of transforming growth factor beta 1 (TGF beta 1) on the survival of embryonic motoneurons in culture. For this purpose, E14 rat embryo motoneurons were purified to more than 90% homogeneity by cell sorting and cultured at low density on monolayers of cortex astrocytes. Subnanomolar concentrations of TGF beta 1 (40-500 pM) increased the survival of motoneurons 2-fold after 9-11 days in culture. The increase in choline acetyltransferase (ChAT) activity per culture caused by TGF beta 1 was attributable to its effects on survival. Comparable results were found with motoneurons cultured on lysed astrocytes, suggesting that the effects of the factor are not mediated by non-neuronal cells, but that motoneurons are a target for TGF beta 1.

Adrenergic Fibers↗
PubMed1990

Transforming growth factor beta (TGF-beta) reverses phorbol diester resistance of a breast adenocarcinoma (MCF-7) subline.

We investigated the effects of TGF-beta on a MCF-7 subline (MCF-7:RPh-4) which is resistant to phorbol diesters with respect to growth inhibition and estrogen receptor content modulation. This biological unresponsiveness of MCF-7:RPh-4 cells to phorbol esters seems to be unrelated to activation of protein kinase C. In the presence of 80 nM PMA (12-O-tetradecanoylphorbol-13-acetate), TGF-beta induced a dose-dependent inhibition of MCF-7:RPh-4 cell proliferation. MCF-7:RPh-4 cells grown in PMA-free medium for at least 28 days remained insensitive to PMA but lost sensitivity to TGF-beta. Under these conditions, addition of 80 nM PMA restored sensitivity to TGF-beta. In the presence of a fixed concentration of TGF-beta, the dose-dependent inhibition of proliferation and the decrease in estrogen receptor content induced by PMA were comparable to those observed in PMA-treated parental MCF-7 cells. These observations indicate that TGF-beta reverses PMA resistance in MCF-7:RPh-4 cells. In addition, TGF-beta does not modify the basal or PMA-stimulated phosphorylation of Mr 28,000 endogenous protein. These results suggest that TGF-beta interferes with the protein kinase C pathway independently of enzyme activation.

Adenocarcinoma↗
PubMed1990

Effects of differentiation-inducing agents on maturation of human MCF-7 breast cancer cells.

The effects of the differentiation inducing agents (DIAS), sodium butyrate (NaBu), retinoic acid (RA), dimethylformamide (DMF), hexamethylene bisacetamide (HMBA), forskolin, and 12-O-tetradecanoylphorbol-13-acetate (TPA), on the growth, morphology, and estrogen receptor (ER) content and epithelial membrane antigen (EMA) expression on a serumless human breast cancer cell line (MCF-7) were compared. All these agents reversibly caused a concentration-dependent growth inhibition in monolayers and markedly reduced colony-forming efficiency in soft agar. A twofold increase in doubling time was obtained with RA (1 microM), but cell replication ceased with NaBu (1 mM), forskolin (50 microM), DMF (1%), HMBA (5 mM), and TPA (8 nM). Total growth arrest induced by these last compounds was preceded by an accumulation of cells in G0/G1 phase observed at 24 h by flow cytometry and accompanied by a change in cell morphology as seen by light and electronic microscopy. An increase in cell volume and the presence of lipid droplets was noted in treated cells that were spread out, as compared with controls. The acquisition of a more mature phenotype was confirmed by an increased expression of EMA monitored by flow cytometry. A specific reduction in the number of ER without any constant dissociation (Kd) modification was also observed after treatment with the 5 DIAs. No modification of morphological or biochemical characteristics, including EMA expression and ER binding, were observed for RA (1 microM)-treated cells. All these results suggest that induction of a more differentiated phenotype is associated with a block in G1 cell cycle phase, resulting in total growth arrest. Apparently, RA (1 microM)-treated cells did not fulfill these criteria, since only a slight accumulation in G1 and a slowed growth rate were evaluated.

Acetamides↗
PubMed1990

Transforming growth factor beta (TGF-beta) potentiates the inhibitory effect of retinoic acid on human breast carcinoma (MCF-7) cell proliferation.

Anchorage-dependent and -independent MCF-7 cell growth was dose-dependently inhibited by retinoic acid (RA) but was insensitive to TGF-beta (from 1 to 100 pM). Growth of MCF-7 monolayer cultures was inhibited (50%) when exposed to 10(-6) M RA. RA was unable to completely inhibit MCF-7 cell proliferation, as concentrations above 10(-6) M were rapidly cytotoxic. However, the combination of TGF-beta and RA resulted an increase in RA inhibitory effect on MCF-7 monolayer growth and a 80% reduction in colony formation in soft agar. These results demonstrate that although TGF-beta does not inhibit the growth of MCF-7 cells, it potentiates the antiproliferative effect of RA, suggesting that it may play a part, albeit indirect, in the regulation of MCF-7 cell growth.

Breast Neoplasms↗
PubMed1988

Modulation of estrogen receptors by phorbol diesters in human breast MCF-7 cell line.

Treatment of MCF-7 cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) results in an inhibition of cell proliferation and a reduction in the number of estrogen receptors (ER), shown by binding studies and immunoassay. The decrease in ER concentration induced by phorbol ester derivatives parallels their growth inhibitory effect. Moreover, the estrogen receptor of TPA-resistant RPh4 cells (which are insensitive to the antiproliferative and morphological effects of TPA) is not affected by TPA treatment. The reduction in ER concentration appear to be a specific phenomenon since it contrasted with the 2-fold increase in total cell protein content which included an increase in progesterone receptor (PgR). We also found that addition of TPA does not affect estrogen induction of PgR.

Binding, Competitive↗
PubMed1987

Influence of 12-O-tetradecanoylphorbol-13-acetate on proliferation and maturation of human breast carcinoma cells (MCF-7): relationship to cell cycle events.

Exposure of MCF-7 human mammary carcinoma cells to 12-O-tetradecanoylphorbol-13-acetate (TPA) results in changes in cell morphology and arrest of cell growth. The inhibition of cell proliferation and the increase in cell volume are concentration dependent; these effects are reversible upon removal of the tumor promoting agent. Electron microscopic studies reveal that TPA increases endoplasmic reticulum and induces the appearance of secretory granules. MCF-7 cells treated by TPA therefore present morphological characteristics of secretory cells. These effects of TPA on MCF-7 cells are accompanied by specific disruption of cell cycle events, a block of cells in G1 at the expense of S base, and a delayed passage through G2. Studies in which a cell cycle lock in G1 is produced by tamoxifen show that exposure of such cells to PA produces cell morphological changes and an inability to progress through the cell cycle when estradiol is added.

Breast Neoplasms↗
PubMed1987

Interaction with lectin of kappa opioid binding sites solubilized from human placenta.

Kappa opioid binding sites from human placenta, prelabeled with 3H-etorphine and solubilized, were retained on wheat germ agglutinin (WGA) agarose and specifically eluted with N-acetylglucosamine. No significant retention was found with other immobilized lectins, including Concanavalin A (Con A), soybean seed lectin (SBA), Pisum sativum lectin (PsA), Lens culinaris Medik. lectin (LcA), and Lathyrus tingitanus lectin(LtA). About 23% of applied kappa sites were specifically eluted from WGA agarose, less than half of the proportion of rat brain opioid binding sites eluted from the same lectin (55%). Receptors from placental extracts were compared with those from other tissues enriched in either kappa or mu sites. The proportion of applied kappa sites from guinea pig cerebellum eluted specifically from WGA agarose was 36%, whereas elution of binding sites from rat thalamus and rabbit cerebellum (enriched in mu sites) was at a level of 55%. This difference in the level of retention on and elution from WGA may reflect differences in the sugar composition of the glycoproteins of the two types of receptors. Succinylation of WGA abolished its ability to retain opioid binding sites, consistent with involvement of sialic acid. However, currently available evidence suggests that differences in retention on WGA between kappa and mu sites may be due to differences in either sialic acid or N-acetylglucosamine content or both.

Acetylglucosamine↗
PubMed1987

Nutritional dependence of the effect of estrogen on fat cell lipoprotein lipase.

We investigated the effects of ethynylestradiol (EE) at low dose (1.2 micrograms/day) injected s.c. for 10 days on lipoprotein lipase (LPL) in fat cells of female rats fed a standard diet (5% lipid, 49.5% glucid, 23.5% protein) as a function of the nutritional state. EE caused a 150% increase in LPL activity in the fed state, and a 65% decrease in the fasting state, resulting in a large increment in the physiological feeding-fasting difference. Feeding the rats a diet supplemented with 20% lard reversed the estrogen-dependent LPL increase in the fed state. Under all experimental conditions, EE caused a depletion of fat stores and an increase in plasma levels of triacyglycerol.

Adipose Tissue↗
PubMed1987

Antiestrogens, different sites of action than the estrogen receptor?

Nonsteroidal antiestrogens display antagonistic as well as agonistic properties when compared with estrogens. These observations and studies of their molecular interactions suggest that part of their activity is mediated through estrogen receptor (ER)-mediated pathways. However, other data, concerning mainly effects on growth and cellular proliferation, cannot be explained on this basis. Recent investigations have shown binding of these molecules to a number of other intracellular binding sites beside ER. Using different cell variants of the human breast cancer cell line MCF-7 we could confirm the peculiar role of one of these sites, the specific antiestrogen-binding site (ABS). Published data on ABS are critically reviewed.

Animals↗
PubMed1986

Phorbol esters inhibit the proliferation of MCF-7 cells. Possible implication of protein kinase C.

The effect of tumor promoter phorbol esters on cell proliferation was investigated in human breast cancer cell line MCF-7. During a 4-day culture period, the various phorbol ester derivatives TPA, PDD, PDBu, PDBz and PDA inhibited the proliferation of MCF-7 cells in a dose-dependent manner, with respective IC50 of 0.06, 0.75, 2.4, 3.6 and 15 X 10(-9) M. The 4-O-met-TPA, alpha PDD and alph PHR were ineffective at 2 X 10(-7) M, the highest concentration tested. Using a 3H-PDBu probe, we demonstrated the presence of specific, high affinity binding sites in intact cultured cells, with a Kd of about 9 X 10(-9) M. Unlabelled TPA, PDD, PDBU and PDBz competed with 3H-PDBu with respective IC50 of 35, 12.5, 150 and 220 X 10(-9) M. High concentrations of PDA, 4-O-met-TPA and alpha PDD slightly inhibited the 3H PDBu binding, whereas alpha PHR did not until 10(-5) M. The correlation that we observed between the relative potencies of the various phorbol derivatives for inhibiting both PDBu binding and cell proliferation, suggests that tumor promoter phorbol esters may induce growth arrest in MCF-7 cells by the mediation of protein kinase C.

Breast Neoplasms↗
PubMed1986

Effects of 2-fluoroestradiol on lipid metabolism in the ovariectomized rat.

Biological activities of estrogen molecules are altered by fluorination of ring A, and the resulting impairment to form catechols. 2-fluoroestradiol (2-F-E2) has been found to be devoid of carcinogenic action despite its high estrogenic potency; its metabolic effects are so far unknown. This study was designed to investigate the effects of 2-F-E2 on lipid metabolism, as compared to those of estradiol-17 beta(E2). Ovariectomized rats received E2 or 2-F-E2 by s.c. injection at a dose of 60 micrograms for three consecutive days. Parameters measured were weights of parametrial fat depots, fat cell volumes, levels of triacylglycerol and acylcholesterol in plasma, and enzymatic responses to the estrogens in isolated parametrial fat cells as evaluated in terms of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities. 2-F-E2 and E2 were found to produce comparable decreases in fat depots, cell volumes and plasma levels of acylcholesterol whereas plasma triacylglycerol was unchanged. Both estrogens decreased LPL, and increased HSL activities to the same extent. Thus, 2-F-E and E2 exhibited comparable effects on lipid metabolism. These effects appeared to depend mainly on the estrogenic potency of these molecules, and to be distinct from their carcinogenic action. Despite its high estrogenic potency, 2-F-E2 was found to be slightly less estrogenic than E2.

Adipose Tissue↗
PubMed1983

Placental kappa binding site : interaction with dynorphin and its possible implication in hCG secretion.

We have previously demonstrated that human placenta contains a homogenous population of kappa binding sites. The selective interaction of dynorphin with these opiate binding sites suggests a possible physiological implication of this endogenous opioid system in the placenta physiology. Ethylketocyclazocine stimulate K+-induced hCG release. This fact favours the hypothesis of a participation of placental opiate receptor on hCG secretion.

Analgesics, Opioid↗
PubMed1983

Purification and identification of multiple forms of dynorphin in human placenta.

Immunoreactive dynorphin (ir-Dyn) and opiate-like peptides (OLP) were measured in acid (HC1) extracts of human placenta by the use of an antibody to synthetic Dyn-(1-13) and of the displacement of [3H]-naloxone binding to rat brain homogenates, respectively. The placenta contained 57.6 pmoles per g of ir-Dyn and 134.4 pmoles per g of naloxone binding equivalents. After passage of the extract through cartridges of Sep Pak C18, half of the OLP was eluted with ir-Dyn at 35% acetonitrile (ACN), the rest being eluted at 60% ACN. Both fractions obtained from Sep Pak were chromatographed separately on Sephadex G-50, the OLP of the 35% ACN fraction coeluting with the ir-Dyn speak and that of the 60% ACN fraction being eluted at the same volume as synthetic beta-endorphin. Conversely, the fraction of OLP coeluting with synthetic leucine-enkephalin (Leu-Enk) in these two chromatographies was minimal. The Dyn-immunoreactive material was further purified by high pressure liquid chromatography on reverse phase micro-Bondapak C18 columns to give three distinct peaks corresponding to synthetic Dyn-(1-11), Dyn-(1-13) and Dyn-(1-12), respectively. Our results indicate that the human placenta contains several forms of ir-Dyn which account for about half of its endogenous OLP.

Animals↗
PubMed1982

Localization of human placental opiate binding sites on the syncytial brush border membrane.

Opiate binding sites were measured in different placental membrane fractions which were characterized by marker enzyme analysis and electron microscopic examination. The distribution pattern of opiate binding sites in the different fractions closely parallels that of placental alkaline phosphatase. These results clearly show that opiate binding sites are mainly located on the syncytial brush border membrane. The opiate binding sites found on microvillus membrane fraction have the same pharmacological characteristics as the Kappa opiate binding site previously characterized on placental crude membrane fraction.

Alkaline Phosphatase↗