Format

Send to

Choose Destination
Oncogene. 2005 Aug 18;24(35):5459-70.

Chronic activation of protein kinase Bbeta/Akt2 leads to multinucleation and cell fusion in human epithelial kidney cells: events associated with tumorigenesis.

Author information

1
Department of Medical Biophysics and Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.

Abstract

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.

PMID:
16007218
DOI:
10.1038/sj.onc.1208704
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center