Inhibition of activated phosphatidylinositol 3-kinase/AKT pathway in malignant pleural mesothelioma leads to G1 cell cycle arrest

  • Authors: Iwao Mikami, Fang Zhang, Tomomi Hirata, Junichi Okamoto, Kiyoshi Koizumi, Kazuo Shimizu, David Jablons, Biao He
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  • Published online on: Wednesday, December 1, 2010
  • Pages: 1677-1681
  • DOI: 10.3892/or_00001033

Abstract

Phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway plays pivotal roles in fundamental cellular functions including cell proliferation and cell survival. Its deregulation has been implicated in many types of human malignancies. We investigated the role of PI3K/AKT signaling pathway in human malignant pleural mesothelioma (MM). Here, we report that aberrant activation of the PI3K/AKT signaling pathway is associated with cell cycle progression in MM cells. Inhibition of the PI3K activity by its small molecule inhibitor LY294002 led to significant G1 cell cycle arrest and suppression of cell proliferation in all MM cell lines that we examined. In addition, we found that the protein level of p27Kip1 was up-regulated and the protein level of cyclin D1 was down-regulated following LY294002 treatment in those MM cell lines. However, no noticeable apoptosis induction was observed following 24 h of LY294002 treatment in those MM cell lines. These results confirm that the PI3K/AKT signaling pathway is aberrantly active and plays a critical role for the cell cycle progression in human MM cells.
Journal Cover

December 2010
Volume 24 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

2012 Impact Factor: 2.297
Ranked #36/196 Oncology
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APA
Mikami, I., Zhang, F., Hirata, T., Okamoto, J., Koizumi, K., Shimizu, K., Jablons, D., & He, B. (2010). Inhibition of activated phosphatidylinositol 3-kinase/AKT pathway in malignant pleural mesothelioma leads to G1 cell cycle arrest . Oncology Reports, 24(6), 1677-1681.
MLA
Mikami, Zhang, Hirata, Okamoto, Koizumi, Shimizu, Jablons, and Biao He. "Inhibition of activated phosphatidylinositol 3-kinase/AKT pathway in malignant pleural mesothelioma leads to G1 cell cycle arrest ." Oncology Reports Oncology Reports 24.6 (2010): 1677-1681.
Chicago
Mikami, Zhang, Hirata, Okamoto, Koizumi, Shimizu, Jablons, and Biao He. "Inhibition of activated phosphatidylinositol 3-kinase/AKT pathway in malignant pleural mesothelioma leads to G1 cell cycle arrest ." Oncology Reports Oncology Reports 24 no. 6 (2010): 1677-1681.