1,720,971 research outputs found
Oxytocin receptor signaling in myoepithelial and cancer cells
No full textOxytocin (OT) plays a crucial role as a mediator of breast myoepithelial cell contraction, the process responsible for the ejection of milk during lactation, and is also involved in myoepithelial cell proliferation and postpartum mammary gland proliferation. Furthermore, although a number of breast cancer cells have oxytocin receptors (OTRs), it has been reported that OT stimulates, inhibits, or has no effect on cell proliferation. As these different effects seem to be mediated by different signaling pathways elicited by OTR stimulation, we here review the regulation of OTR signaling in different cell systems and discuss how understanding the molecular basis of receptor coupling specificity has become extremely important for understanding the role played by OTRs in regulating cell growth
Accoppiamento del recettore per l'ossitocina a varie proteine G : identificazione di un composto selettivo per una singola via di trasduzione del segnale
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Effects of cholesterol manipulation on the signaling of the human oxytocin receptor
No full textWe have recently shown that oxytocin inhibits cell growth when the vast majority of oxytocin receptors (OTRs) are excluded from detergent-resistant membranes (DRMs; the biochemical counterpart of lipid rafts), but has a strong mitogenic effect when the receptors are targeted to these plasma membrane domains upon fusion with caveolin-2, a resident raft protein. The aim of this study was to investigate whether the manipulation of total cell cholesterol can influence OTR localization and signaling. Our data indicate that cholesterol depletion in HEK-293 cells does not affect the signaling events mediated by the OTRs located outside DRMs. When treated with 2 mM methyl-beta-cyclodextrin (MbetaCD), the receptors remained outside and continued to inhibit cell growth. On the contrary, the MbetaCD treatment of cells expressing receptors fused to caveolin-2 led to their redistribution outside DRMs, and converted the receptor-mediated proliferative effect into cell growth inhibition. These data indicate that 1) once released from DRMs, the receptors fused to caveolin-2 signal exactly as wild-type OTRs and 2) their DRM location is responsible for the specific OTR signaling leading to cell proliferation. Finally, we evaluated whether cholesterol loading could force the OTRs into lipid rafts and change their signaling, but, after cell treatment with an MbetaCD/cholesterol complex, receptor stimulation continued to lead to cell growth inhibition, thus indicating that increasing cell cholesterol levels is not sufficient per se to affect OTR signaling
Oxytocin-mediated control of cell proliferation : role of oxytocin receptor localization in lipid rafts
No full textLocalization in caveolin-1 enriched domains modulates the oxytocin receptor mediated effects on cell growth
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Oxytocin receptor elicits different EGFR/MAPK activation patterns depending on its localisation in caveolin-1 microdomains
No full textOxytocin receptor elicits different EGFR/MAPK activation patterns depending on its localisation in caveolin-1 enriched domains
No full textWe have recently shown that oxytocin inhibits cell proliferation when the vast majority of oxytocin receptors are excluded from caveolin-1-enriched microdomains, and that, on the contrary, it has a mitogenic effect when the receptors are targeted to these plasma membrane domains. In this study, we investigated whether the receptors located inside and outside caveolar microdomains initiate different signalling pathways and how this may lead to opposite effects on cell proliferation. Our data indicate that, depending on their localization, oxytocin receptors transactivate EGFR and activate ERK1/2 using different signalling intermediates. The final outcome is a different temporal pattern of EGFR and ERK1/2 phosphorylation, which is more persistent when the receptors are located outside caveolar microdomains and inhibit cell growth, and very transient when they are located in caveolar microdomains and stimulate cell growth. Finally, only the activation of receptors located outside caveolar microdomains correlates with the activation of the cell cycle inhibitor p21(WAF1/CIP1), thus suggesting that the antiproliferative OTR effects may, in this case, be achieved by a sustained activation of EGFR and MAPK leading to the induction of this cell cycle regulator
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