The compound 3l is an indole-derivative, capable of inducing a strong and irreversible G0/G1 cell cycle arrest without showing any cytotoxicity in human ovarian carcinoma cells, IGROV-1. Estrogen receptors (ERs) are represented by a family of nuclear transcription factors that, upon binding with estrogenic ligands, such as b-estradiol (E2), bind to DNA and modulate target gene expression. In the classical signalling pathway, upon activation by estrogens, ERs, both as homodimers or heterodimers, bind directly to estrogen responsive elements (EREs) located at the promoters of many estrogen-responsive genes. In particular, E2 activation of ERa leads to enhanced cell proliferation, mediated by gene transcription induction; whereas activated ERb negatively affects gene transcription, acting as a tumor suppressor in several cancer cells. In addition, both genomic and non-genomic non-classical ER pathways have been described. Ligand-bound ERs can modulate ERE-independent gene transcription by interacting with other transcription factors, such as AP-1. Alternatively, gene expression modulation can occur in the absence of estrogenic ligands: in this case, ER activation is triggered by growth factor (GF) pathways and is mediated by ER phosphorylation. Non-genomic pathway involves cytoplasmic and plasma membrane associated ERs, which activation depends on other membrane receptors transactivation, like IGF-IR and EGFR, and leads to further signal transduction, such as AKT or MAPK pathways.

THE INDOLE-DERIVATIVE 3L INTERFERES WITH ESTROGEN RECEPTOR SIGNALLING IN IGROV 1 OVARIAN CANCER CELLS

PAROLIN, CAROLA ELEONORA;CALONGHI, NATALIA;CAPPADONE, CONCETTINA;SARTOR, GIORGIO;ANDREANI, ALDO;MASOTTI, LANFRANCO
2010

Abstract

The compound 3l is an indole-derivative, capable of inducing a strong and irreversible G0/G1 cell cycle arrest without showing any cytotoxicity in human ovarian carcinoma cells, IGROV-1. Estrogen receptors (ERs) are represented by a family of nuclear transcription factors that, upon binding with estrogenic ligands, such as b-estradiol (E2), bind to DNA and modulate target gene expression. In the classical signalling pathway, upon activation by estrogens, ERs, both as homodimers or heterodimers, bind directly to estrogen responsive elements (EREs) located at the promoters of many estrogen-responsive genes. In particular, E2 activation of ERa leads to enhanced cell proliferation, mediated by gene transcription induction; whereas activated ERb negatively affects gene transcription, acting as a tumor suppressor in several cancer cells. In addition, both genomic and non-genomic non-classical ER pathways have been described. Ligand-bound ERs can modulate ERE-independent gene transcription by interacting with other transcription factors, such as AP-1. Alternatively, gene expression modulation can occur in the absence of estrogenic ligands: in this case, ER activation is triggered by growth factor (GF) pathways and is mediated by ER phosphorylation. Non-genomic pathway involves cytoplasmic and plasma membrane associated ERs, which activation depends on other membrane receptors transactivation, like IGF-IR and EGFR, and leads to further signal transduction, such as AKT or MAPK pathways.
55th National Meeting of the Italian Society of Biochemistry and Molecular Biology (SIB)
66
66
Parolin C.; Calonghi N.; Cappadone C.; Sartor G.; Andreani A.; Masotti L.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/101355
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