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Cobalt chloride stimulates phosphoinositide 3-kinase/Akt signaling through the epidermal growth factor receptor in oral squamous cell carcinoma

MI HEON RYU1,a, JEONG HEE PARK1,a, JI EUN PARK1, JIN CHUNG2, CHANG HUN LEE3AND HAE RYOUN PARK1*
1. Department of Oral Pathology, School of Dentistry, Pusan National University, Beomeo-ri, Mulgeum-Eup, Yangsan 626870, South Korea
2. Department of Oral Microbiology, School of Dentistry, Pusan National University, Beomeo-ri, Mulgeum-Eup, Yangsan 626-870, South Korea
3. Department of Pathology, School of Medicine, Pusan National University, Beomo-ri, Mulgeum-Eup, Yangsan, South Korea
a.These authors contributed equally to this work.
*Address correspondence to: Hae Ryoun Park. E-mail:

BIOCELL 2010, 34(1), 15-22. https://doi.org/10.32604/biocell.2010.34.015

Abstract

Tumor cells are often found under hypoxic conditions due to the rapid outgrowth of their vascular supply, and, in order to survive hypoxia, these cells induce numerous signaling factors. Akt is an important kinase in cell survival, and its activity is regulated by the upstream phosphoinositide 3-kinase (PI3K) and receptor tyrosine kinases (RTKs). In this study, we examined Akt activation and RTKs/PI3K/Akt signaling using the hypoxia-mimetic cobalt chloride in oral squamous carcinoma cells. Cobalt chloride increases Akt phosphorylation in both a dose- and time-dependent manner. Blocking the activation of the PI3K/Akt pathway using LY294002 abolished Akt activation in response to cobalt chloride, suggesting that Akt phosphorylation by cobalt chloride is dependent on PI3K. In addition, activation of the PI3K/Akt pathway seems to rely on the epidermal growth factor receptor (EGFR), since the inhibition of EGFR attenuated cobalt chloride-induced Akt activation. The results in this study also demonstrate that cobalt chloride increases EGFR protein levels and induces oral squamous cell carcinoma cells to enter S phase.

Keywords

hypoxia, DNA synthesis, S-phase

Cite This Article

RYU, M. H., PARK, J. H., PARK, J. E., CHUNG, J., LEE, C. H. (2010). Cobalt chloride stimulates phosphoinositide 3-kinase/Akt signaling through the epidermal growth factor receptor in oral squamous cell carcinoma. BIOCELL, 34(1), 15–22.

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This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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