Abstract:
:Growth hormone receptor (GHR) has been demonstrated to be nuclear localized both in vivo and in vitro, but the significance of this observation has remained elusive. Here we show that nuclear GHR is strongly correlated with proliferative status in vivo by using a liver regeneration model. In vitro, nuclear translocation of the GH receptor is GH-dependent and appears to be mediated by the Importin system. Constitutive nuclear targeting of GHR in murine pro-B cells is associated with constitutive activation of STAT5, a transforming agent in lymphoma and other cell types. This activation is abrogated by inhibition of JAK2 and appears to be driven by autocrine murine GH action coupled with enhanced nuclear uptake of phospho-STAT5. Nuclear targeting induces dysregulated cell cycle progression in the pro-B cell line, associated with constitutive up-regulation of the proliferation inducers Survivin and Mybbp, the metastasis related Dysadherin, and other tumor markers. GHR nuclear-targeted cells generate aggressive metastatic tumors when injected into nude mice, which display nuclear localized GHR strikingly similar to that seen in human lymphomas. We conclude that aberrant nuclear localization of GHR is a marker of high proliferative status and is sufficient to induce tumorigenesis and tumor progression.
journal_name
Proc Natl Acad Sci U S Aauthors
Conway-Campbell BL,Wooh JW,Brooks AJ,Gordon D,Brown RJ,Lichanska AM,Chin HS,Barton CL,Boyle GM,Parsons PG,Jans DA,Waters MJdoi
10.1073/pnas.0600181104subject
Has Abstractpub_date
2007-08-14 00:00:00pages
13331-6issue
33eissn
0027-8424issn
1091-6490pii
0600181104journal_volume
104pub_type
杂志文章abstract::The search for ever deeper relationships among the World's languages is bedeviled by the fact that most words evolve too rapidly to preserve evidence of their ancestry beyond 5,000 to 9,000 y. On the other hand, quantitative modeling indicates that some "ultraconserved" words exist that might be used to find evidence ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2013-05-21 00:00:00
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