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Src is an initial target of sex steroid hormone action
A Migliaccio1, G Castoria, M Di Domenico
1Istituto di Patologia Generale e Oncologia, Seconda Università di Napoli, 80138 Naples, Italy.
Abstract:
Recent observations that steroids use pathways universally known to be regulated by growth factors and interleukins highlight the following points: (1) Steroid stimulation of the canonical pathway Src/Ras/Erk signaling from membrane to nuclei or its single members has been observed in different cell types including human cancer-derived cells, neurons, osteoblasts, osteocytes, and endothelial cells. This stimulation has been reconstituted and analyzed in transiently transfected cells. (2) Cellular context and intracellular localization of receptors are crucial in determining the biological effects evoked by this hormonal stimulation: proliferation, protection from apoptosis, and vasorelaxation. (3) Classical steroid receptors localized in the extranuclear compartment directly and, in some cases, simultaneously interact with Src. They are capable of unexpected cross talks responsible for the observed effects. (4) Other signaling pathways including P13K/AKT are also stimulated by steroids. The aim of future work will be to arrive at an integrated general view of the different signaling pathways activated by steroids and to analyze the concert between these pathways and the hormonal transcriptional action. This general view should be simultaneously verified in different cell contexts, under different physiologic and pathologic conditions. We expect that the new technologies, above all gene and protein microarray, will make this goal feasible.
Insights
Steroids activate key cell signaling pathways like Src/Ras/Erk and P13K/AKT, influencing cell behavior. Receptor location and cellular context determine steroid-induced effects such as proliferation and apoptosis protection.
Area of Science:
- Cellular biology
- Molecular endocrinology
- Signal transduction
Background:
- Steroids are known to regulate cellular functions through various pathways.
- Recent findings indicate steroid involvement in pathways typically controlled by growth factors and interleukins.
- Understanding these non-classical steroid actions is crucial for comprehending cellular responses.
Purpose of the Study:
- To investigate the role of steroids in activating signaling pathways.
- To elucidate the mechanisms underlying steroid-induced cellular effects.
- To explore the interplay between steroid signaling and cellular context.
Main Methods:
- Observation of steroid stimulation in diverse cell types, including human cancer cells, neurons, and endothelial cells.
- Reconstitution and analysis of signaling pathways in transiently transfected cells.
- Investigation of classical steroid receptor interactions with Src in extranuclear compartments.
Main Results:
- Steroid stimulation of the Src/Ras/Erk pathway was observed across multiple cell types.
- Cellular context and receptor localization critically influence steroid-mediated effects like proliferation and apoptosis protection.
- Extranuclear steroid receptors directly interact with Src, mediating cross-talk and biological responses.
- Steroids also activate other pathways, such as P13K/AKT.
Conclusions:
- Steroids utilize and modulate signaling pathways traditionally associated with growth factors and interleukins.
- The cellular environment and receptor localization are key determinants of steroid-induced biological outcomes.
- Future research aims to integrate these findings into a comprehensive model of steroid signaling.