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

Oncogene volume 24, pages 5459–5470 (2005)Cite this article

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 PKBβ, the activation of which is under the control of a 4-hydroxy-Tamoxifen-responsive estrogen-receptor (ER) ligand binding domain. Induction of PKBβ-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 PKBβ-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 PKBβ may contribute to genetic instability and autophagy, properties commonly found in tumor cells.

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Acknowledgements

This work was supported by a grant from the National Cancer Institute of Canada/Canadian Cancer Society. We thank Roberta Siu, Mike Parsons, Mike Scheid, Battista Calvieri and James Jonkman for their valuable advice and assistance.

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  1. Jing Jin

    Present address: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada

Authors and Affiliations

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

    Jing Jin & James R Woodgett

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Correspondence to James R Woodgett.

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Jin, J., Woodgett, J. Chronic activation of protein kinase Bβ/Akt2 leads to multinucleation and cell fusion in human epithelial kidney cells: events associated with tumorigenesis. Oncogene 24, 5459–5470 (2005). https://doi.org/10.1038/sj.onc.1208704

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