Linked Life Data

17699780

Source:http://linkedlifedata.com/resource/pubmed/id/17699780

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2007-8-16
pubmed:abstractText
Glycogen synthase kinase 3beta (GSK3beta) is a multifunctional serine/threonine kinase. We showed that the expression of GSK3beta was drastically down-regulated in human cutaneous squamous cell carcinomas and basal cell carcinomas. Due to its negative regulation of many oncogenic proteins, we hypothesized that GSK3beta may function as a tumor suppressor during the neoplastic transformation of epidermal cells. We tested this hypothesis using an in vitro model system, JB6 mouse epidermal cells. In response to epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA), the promotion-sensitive JB6 P+ cells initiate neoplastic transformation, whereas the promotion-resistant JB6 P- cells do not. JB6 P- cells expressed much higher levels of GSK3beta than JB6 P+ cells; JB7 cells, the transformed derivatives of JB6, had the least amount of GSK3beta. The activity of GSK3beta is negatively regulated by its phosphorylation at Ser9. EGF and TPA induced strong Ser9 phoshorylation in JB6 P+ cells, but phosphorylation was seen at a much lesser extent in JB6 P- cells. EGF and TPA-stimulated Ser9 phosphorylation was mediated by phosphoinositide-3-kinase (PI3K)/Akt and protein kinase C (PKC) pathways. Inhibition of GSK3beta activation significantly stimulated activator protein-1 (AP-1) activity. Overexpression of wild-type (WT) and S9A mutant GSK3beta in JB6 P+ cells suppressed EGF and TPA-mediated anchorage-independent growth in soft agar and tumorigenicity in nude mice. Overexpression of a kinase-deficient (K85R) GSK3beta, in contrast, potentiated anchorage-independent growth and drastically enhanced in vivo tumorigenicity. Together, these results indicate that GSK3beta plays an important role in skin tumorigenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7756-64
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:17699780-Animals, pubmed-meshheading:17699780-Carcinoma, Basal Cell, pubmed-meshheading:17699780-Carcinoma, Squamous Cell, pubmed-meshheading:17699780-Cell Transformation, Neoplastic, pubmed-meshheading:17699780-Enzyme Activation, pubmed-meshheading:17699780-Epidermal Growth Factor, pubmed-meshheading:17699780-Glycogen Synthase Kinase 3, pubmed-meshheading:17699780-Humans, pubmed-meshheading:17699780-Male, pubmed-meshheading:17699780-Mice, pubmed-meshheading:17699780-Mice, Inbred BALB C, pubmed-meshheading:17699780-Oncogene Protein v-akt, pubmed-meshheading:17699780-Phosphatidylinositol 3-Kinases, pubmed-meshheading:17699780-Protein Kinase C, pubmed-meshheading:17699780-Signal Transduction, pubmed-meshheading:17699780-Skin, pubmed-meshheading:17699780-Skin Neoplasms, pubmed-meshheading:17699780-Tetradecanoylphorbol Acetate, pubmed-meshheading:17699780-Transcription Factor AP-1, pubmed-meshheading:17699780-Transfection
pubmed:year
2007
pubmed:articleTitle
The role of glycogen synthase kinase 3beta in the transformation of epidermal cells.
pubmed:affiliation
Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Robert C. Byrd Health Sciences Center, Morgantown, WV, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural