Chronic activation of protein kinase Bβ/Akt2 leads to multinucleation and cell fusion in human epithelial kidney cells

Events associated with tumorigenesis

Jing Jin, James R. Woodgett*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 protooncogene 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.

Original languageEnglish (US)
Pages (from-to)5459-5470
Number of pages12
JournalOncogene
Volume24
Issue number35
DOIs
StatePublished - Aug 18 2005

Fingerprint

Proto-Oncogene Proteins c-akt
Cell Fusion
Carcinogenesis
Epithelial Cells
Kidney
Estrogen Receptors
Phosphatidylinositol 3-Kinase
Neoplasms
Autophagy
Aneuploidy
Diploidy
Human Activities
Cell Movement
Cell Survival
Cell Cycle
Chromosomes
Maintenance
Ligands
Membranes
Growth

Keywords

  • Akt
  • Autophagy
  • Cell fusion
  • Cytokinesis
  • Endomitosis/endoreplication
  • PKB
  • Phagocytosis
  • Pinocytosis
  • Tamoxifen-induced
  • Tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

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title = "Chronic activation of protein kinase Bβ/Akt2 leads to multinucleation and cell fusion in human epithelial kidney cells: Events associated with tumorigenesis",
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 protooncogene 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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Chronic activation of protein kinase Bβ/Akt2 leads to multinucleation and cell fusion in human epithelial kidney cells : Events associated with tumorigenesis. / Jin, Jing; Woodgett, James R.

In: Oncogene, Vol. 24, No. 35, 18.08.2005, p. 5459-5470.

Research output: Contribution to journalArticle

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