Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-2-20
pubmed:abstractText
We generated a p27(Kip1) mutant (p27deltaNLS) that localized exclusively in cell cytosol. Expression of p27deltaNLS in MCF7 breast cancer cells down-regulated RhoA and increased motility, survival, and Akt levels without an effect on cell cycle distribution. RNA interference of p27 in U87 glioma cells, which express p27 predominantly in the cytoplasm, inhibited motility and survival. Conversely, knockdown of p27 in COS7 cells, with >95% nuclear p27 expression, accelerated proliferation but had no effect on motility or survival. U87 cells in which p27 had been eliminated by RNA interference exhibited lower Akt levels, shorter Akt turnover, and markedly impaired tumorigenicity in vivo. These xenografts were less invasive and exhibited increased apoptosis compared with p27-expressing tumors. Expression of cytosolic p27 in primary human breast carcinomas correlated linearly with Akt content as measured by immunohistochemistry. These data suggest that cytoplasmic p27 can exert oncogenic functions by modulating Akt stability, cell survival, and tumorigenicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2162-72
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16489017-Amino Acid Sequence, pubmed-meshheading:16489017-Animals, pubmed-meshheading:16489017-Breast Neoplasms, pubmed-meshheading:16489017-COS Cells, pubmed-meshheading:16489017-Cell Adhesion, pubmed-meshheading:16489017-Cell Movement, pubmed-meshheading:16489017-Cell Survival, pubmed-meshheading:16489017-Cercopithecus aethiops, pubmed-meshheading:16489017-Cyclin-Dependent Kinase Inhibitor p27, pubmed-meshheading:16489017-Cytosol, pubmed-meshheading:16489017-Down-Regulation, pubmed-meshheading:16489017-Glioma, pubmed-meshheading:16489017-Humans, pubmed-meshheading:16489017-Mice, pubmed-meshheading:16489017-Mice, Nude, pubmed-meshheading:16489017-Molecular Sequence Data, pubmed-meshheading:16489017-Neoplasm Transplantation, pubmed-meshheading:16489017-Proto-Oncogene Proteins c-akt, pubmed-meshheading:16489017-RNA Interference, pubmed-meshheading:16489017-Transfection, pubmed-meshheading:16489017-Transplantation, Heterologous, pubmed-meshheading:16489017-rhoA GTP-Binding Protein
pubmed:year
2006
pubmed:articleTitle
Reduction of cytosolic p27(Kip1) inhibits cancer cell motility, survival, and tumorigenicity.
pubmed:affiliation
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural