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http://hdl.handle.net/10261/78753
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dc.contributor.author | Domínguez-Cáceres, Mª Aurora | - |
dc.contributor.author | García-Martínez, José Manuel | - |
dc.contributor.author | Calcabrini, Annarica | - |
dc.contributor.author | González, Lorena | - |
dc.contributor.author | González-Porque, Pedro | - |
dc.contributor.author | León, Javier | - |
dc.contributor.author | Martín-Pérez, Jorge | - |
dc.date.accessioned | 2013-06-28T08:12:47Z | - |
dc.date.available | 2013-06-28T08:12:47Z | - |
dc.date.issued | 2004 | - |
dc.identifier | doi: 10.1038/sj.onc.1208002 | - |
dc.identifier | issn: 0950-9232 | - |
dc.identifier | e-issn: 1476-5594 | - |
dc.identifier.citation | Oncogene 23(44): 7378-7390 (2004) | - |
dc.identifier.uri | http://hdl.handle.net/10261/78753 | - |
dc.description.abstract | Stimulation of resting W53 cells (lymphoid murine cells expressing prolactin (PRL) receptor) by PRL induced expression of growth-related immediate-early genes (IEG), and proliferation through activation of the Src kinases. Since IEG are essential for cell cycle progression, we have studied how PRL controls expression of c-Myc mRNA and c-Fos. Stimulation of W53 cell proliferation by PRL required activation of MAPK, as the Mek1/2 inhibitor PD184352 eliminated Erk1/2 stimulation, cell proliferation, and expression of c-Fos mRNA. In contrast, PD184352 did not alter PRL activation of c-Myc mRNA expression or stimulation of p70S6K, Akt, and the Jak2/ Stat5 pathway. Activation of the PI3K by PRL was necessary for the expression of c-Myc mRNA and W53 cell proliferation, as the PI3K inhibitor LY294002 abolished them. However, it did not modify PRL stimulation of c-Fos mRNA expression or activation of Erk1/2 and Stat5. Furthermore, rapamycin, an inhibitor of mTOR and consequently of p70S6K, did not alter PRL stimulation of c-Myc and c-Fos mRNA expression and it had a very minor inhibitory effect on PRL stimulation of W53 cell proliferation. In addition, rapamycin did not affect PRL stimulation of Akt or Stat5. However, it reinforced PRL activation of Erk1/2. Overexpression of a constitutively activated Akt (myristoylated Akt) in W53 cells overcame the inhibitory effect of LY294002 on c-Myc expression, as well as cell death upon PRL deprivation. Consistently, inducible expression of Akt-CAAX Box in W53 cells caused inhibition of c-Myc expression. PRL stimulation of W53 cells resulted in Akt translocation to the nucleus, phosphorylation of FKHRL1 transcription factor, and its nuclear exclusion. In contrast, induced expression of Akt-CAAX Box caused inhibition of FKHRL1 phosphorylation. Furthermore, transient expression of nonphosphorylatable FKHRL1-A3 mutant impaired PRL-induced activation of the c-Myc promoter. Akt activation also resulted in phosphorylation and inhibition of glycogen synthetase kinase 3 (GSK3), which in turn promoted c-Myc stability. Consistently, treatment of W53 with selective inhibitors of GSK3 such as SB415286 and lithium salts resulted in increased levels of c-Myc. Also, overexpression of c-Myc in W53 cells overcame the decrease in cell proliferation induced by LY294002. These findings defined a PRL-signalling cascade in W53 cells, involving Src kinases/PI3K/Akt/ FKHRL1-GSK3, that mediates stimulation of c-Myc expression. | - |
dc.description.sponsorship | This work was supported by grants to J.M.-P from MCyT (PM99-0113, SAF2003-02188), CAM (08.1/0047/98) and FIS (01/1316), and grant to J.L. from MCyT (SAF2002-4193). J.M.G.M. was supported by a fellowship from FIS and L.G. was supported by a fellowship from Fundación Carolina. | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.rights | closedAccess | - |
dc.title | Prolactin induces c-Myc expression and cell survival through activation of Src/Akt pathway in lymphoid cells | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1038/sj.onc.1208002 | - |
dc.date.updated | 2013-06-28T08:12:47Z | - |
dc.description.version | Peer Reviewed | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
item.languageiso639-1 | en | - |
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