Linked Life Data

11719430

Source:http://linkedlifedata.com/resource/pubmed/id/11719430

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2001-11-23
pubmed:abstractText
The oncogenic protein Ski associates with Smad proteins and counteracts their activation of gene expression and growth inhibition in response to transforming growth factor beta (TGF-beta). Here we show that Ski protein levels are increased in all 44 human melanoma tumor tissues analyzed in vivo. In addition, Ski subcellular localization changes from nuclear, in preinvasive melanomas (melanomas in situ), to nuclear and cytoplasmic in primary invasive and metastatic melanomas. Furthermore, Ski/Smad association in the cytoplasm seems to prevent Smad3 nuclear translocation in response to TGF-beta. The biological significance of Ski overexpression in melanomas was established by showing that down-regulation of Ski levels, by antisense Ski vectors, restored TGF-beta-mediated growth inhibition. Such inhibition is apparently mediated by up-regulation of the cyclin-dependent kinase-I p21(Waf-1) and inhibition of cyclin-dependent kinase 2 activity. Our results suggest that high levels of Ski in human melanomas produce a disruption of TGF-beta signaling phenotypically similar to that in cells harboring mutations in TGF-beta receptors or Smad proteins, and this may represent a significant event in the progression of melanomas in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8074-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Cytoplasmic localization of the oncogenic protein Ski in human cutaneous melanomas in vivo: functional implications for transforming growth factor beta signaling.
pubmed:affiliation
Department of Dermatology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't