Document Detail


Chronic activation of protein kinase Bbeta/Akt2 leads to multinucleation and cell fusion in human epithelial kidney cells: events associated with tumorigenesis.
MedLine Citation:
PMID:  16007218     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Most cancers arise from the stepwise accumulation of genetic changes. There is also evidence for defects in the machinery and checkpoints for maintenance of normal diploid chromosome complements, resulting in genetic instability that helps fuel the accumulation of mutations that contribute to the development of cancer. The proto-oncogene protein kinase B (PKB/Akt), and its regulators including phosphatidylinositol 3' kinase and PTEN, has been shown to play critical roles in the regulation of multiple cellular functions such as transcription, cell survival, cell cycle progression, angiogenesis and cell motility--all of which are important to the malignant process. Here, we report the use of a membrane targeted PKBbeta, the activation of which is under the control of a 4-hydroxy-Tamoxifen-responsive estrogen-receptor (ER) ligand binding domain. Induction of PKBbeta-ER activity in human kidney epithelial cells (HEK293) resulted in changes in cellular growth, size, and in the appearance of aneuploid cells. Over time, in a PKBbeta-dependent manner, cells also underwent extensive multinucleation caused due to a combination of both endomitosis and cell fusion. These findings suggest that chronic activation of PKBbeta may contribute to genetic instability and autophagy, properties commonly found in tumor cells.
Authors:
Jing Jin; James R Woodgett
Related Documents :
14716738 - Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes...
7526888 - Inverse relationships between cell proliferation and basal or androgen-stimulated apoli...
7536668 - Growth of lncap human prostate cancer cells is stimulated by estradiol via its own rece...
20368938 - Apoptotic effect of ip(6) was not enhanced by co-treatment with myo-inositol in prostat...
6833178 - Comparison of cytochromes from anaerobically and aerobically grown cells of pseudomonas...
3754788 - Circumvention of deficient activation in mitomycin c-resistant human colonic carcinoma ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  24     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-08-19     Completed Date:  2005-09-15     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  5459-70     Citation Subset:  IM    
Affiliation:
Department of Medical Biophysics and Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cell Fusion
Cell Line
Cell Transformation, Neoplastic / drug effects,  metabolism*,  ultrastructure
Enzyme Activation / drug effects,  physiology*
Epithelial Cells / drug effects,  enzymology*,  pathology
Estrogen Antagonists / pharmacology
Humans
Microscopy, Electron, Transmission
Protein-Serine-Threonine Kinases / drug effects,  metabolism*
Proto-Oncogene Proteins / drug effects,  metabolism*
Proto-Oncogene Proteins c-akt
Receptors, Estrogen / metabolism
Recombinant Fusion Proteins / metabolism
Tamoxifen / analogs & derivatives,  pharmacology
Chemical
Reg. No./Substance:
0/Estrogen Antagonists; 0/Proto-Oncogene Proteins; 0/Receptors, Estrogen; 0/Recombinant Fusion Proteins; 10540-29-1/Tamoxifen; 17197F0KYM/afimoxifene; EC 2.7.11.1/AKT1 protein, human; EC 2.7.11.1/AKT2 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Id2 protein is selectively upregulated by UVB in primary, but not in immortalized human keratinocyte...
Next Document:  Maspin sensitizes prostate cancer cells to doxazosin-induced apoptosis.