ERK activation and subsequent RB phosphorylation are important determinants of the sensitivity to paclitaxel in lung adenocarcinoma cells

  • Authors:
    • Hisashi Suyama
    • Tadashi Igishi
    • Hiroyuki Sano
    • Shingo Matsumoto
    • Yasushi Shigeoka
    • Hirofumi Nakanishi
    • Masahiro Endo
    • Naoto Burioka
    • Yutaka Hitsuda
    • Eiji Shimizu
  • View Affiliations

  • Published online on: June 1, 2004     https://doi.org/10.3892/ijo.24.6.1499
  • Pages: 1499-1504
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Abstract

Paclitaxel is used frequently in the treatment of advanced non-small cell lung cancer. This study was carried out in order to determine the role of extracellular signal-regulated kinases (ERK) and retinoblastoma protein (pRB) in the governing mechanism resistance to paclitaxel using two lung adenocarcinoma cell lines with differing sensitivities. In paclitaxel-sensitive Ma-10 cells, treatment with paclitaxel induced pRB phosphorylation at Ser795 and ERK activation. In contrast, in paclitaxel-resistant Ma-31 cells, paclitaxel dephosphorylated pRB at Ser795 without affecting ERK activity. A specific ERK inhibitor, PD98059, blocked paclitaxel-induced ERK activation and pRB phosphorylation at Ser795 in Ma-10 cells. Furthermore, PD98059 inhibited cell cycle progression during paclitaxel treatment, the accumulation of sub-G1 population, and the cytotoxic effect by paclitaxel in Ma-10 cells, suggesting that ERK activation by paclitaxel, subsequent pRB phosphorylation, and the cell cycle progression during paclitaxel treatment are important determinants of sensitivity to paclitaxel. These observations raise the possibility that the promotion of cell cycle during the exposure of lung cancer cells to paclitaxel may sensitize resistant cells to paclitaxel.

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June 2004
Volume 24 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Suyama H, Igishi T, Sano H, Matsumoto S, Shigeoka Y, Nakanishi H, Endo M, Burioka N, Hitsuda Y, Shimizu E, Shimizu E, et al: ERK activation and subsequent RB phosphorylation are important determinants of the sensitivity to paclitaxel in lung adenocarcinoma cells. Int J Oncol 24: 1499-1504, 2004
APA
Suyama, H., Igishi, T., Sano, H., Matsumoto, S., Shigeoka, Y., Nakanishi, H. ... Shimizu, E. (2004). ERK activation and subsequent RB phosphorylation are important determinants of the sensitivity to paclitaxel in lung adenocarcinoma cells. International Journal of Oncology, 24, 1499-1504. https://doi.org/10.3892/ijo.24.6.1499
MLA
Suyama, H., Igishi, T., Sano, H., Matsumoto, S., Shigeoka, Y., Nakanishi, H., Endo, M., Burioka, N., Hitsuda, Y., Shimizu, E."ERK activation and subsequent RB phosphorylation are important determinants of the sensitivity to paclitaxel in lung adenocarcinoma cells". International Journal of Oncology 24.6 (2004): 1499-1504.
Chicago
Suyama, H., Igishi, T., Sano, H., Matsumoto, S., Shigeoka, Y., Nakanishi, H., Endo, M., Burioka, N., Hitsuda, Y., Shimizu, E."ERK activation and subsequent RB phosphorylation are important determinants of the sensitivity to paclitaxel in lung adenocarcinoma cells". International Journal of Oncology 24, no. 6 (2004): 1499-1504. https://doi.org/10.3892/ijo.24.6.1499