Diverse activation states of RhoA in human lung cancer cells: Contribution of G protein coupled receptors

  • Authors:
    • Hirokazu Touge
    • Hiroki Chikumi
    • Tadashi Igishi
    • Jun Kurai
    • Haruhiko Makino
    • Yoshisato Tamura
    • Miyako Takata
    • Kazuhiko Yoneda
    • Masaki Nakamoto
    • Hisashi Suyama
    • J. Silvio Gutkind
    • Eiji Shimizu
  • View Affiliations

  • Published online on: March 1, 2007     https://doi.org/10.3892/ijo.30.3.709
  • Pages: 709-715
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Abstract

Rho GTPases play an essential role in the control of various cellular functions. Accumulating evidence suggests that RhoA overexpression contributes to human cancer development. However, the activation states of RhoA are poorly defined in cancer cells. In this study, we examined both the expression levels and the activation states of RhoA in various lung cancer cells by quantitative real-time reverse transcriptase-polymerase chain reaction and in vivo Rho guanine nucleotide exchange assay, respectively. Moreover, we dissected the signaling pathway from the cell surface receptors to RhoA using a broad-spectrum G protein coupled receptor (GPCR) antagonist, [D-Arg1,D-Trp5,7,9,Leu11]Substance P (SP), and a recently reported Gαq/11-selective inhibitor, YM-254890. We found that RhoA was expressed highly in large cell carcinoma cells but only weakly in adenocarcinoma cells. The activation states of RhoA are considerably different from its expression profiles. We found that four of six small cell lung carcinoma (SCLC) cell lines exhibited a moderate to high activation rate of RhoA. The addition of [D-Arg1,D-Trp5,7,9,Leu11]SP reduced RhoA activity by almost 60% in H69 SCLC cells. The addition of YM-254890 had no effect on RhoA activity in H69 cells. Our results suggest that RhoA is activated in various lung cancer cells independent of its expression levels, and the high activation state of RhoA in SCLC cells mainly depends on a neuroendocrine peptide autocrine system which signals through Gα12 coupled GPCR to RhoA. This study provides new insights into RhoA signaling in lung cancer cells and may help in developing novel therapeutic strategies against lung cancer.

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March 2007
Volume 30 Issue 3

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

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Spandidos Publications style
Touge H, Chikumi H, Igishi T, Kurai J, Makino H, Tamura Y, Takata M, Yoneda K, Nakamoto M, Suyama H, Suyama H, et al: Diverse activation states of RhoA in human lung cancer cells: Contribution of G protein coupled receptors. Int J Oncol 30: 709-715, 2007
APA
Touge, H., Chikumi, H., Igishi, T., Kurai, J., Makino, H., Tamura, Y. ... Shimizu, E. (2007). Diverse activation states of RhoA in human lung cancer cells: Contribution of G protein coupled receptors. International Journal of Oncology, 30, 709-715. https://doi.org/10.3892/ijo.30.3.709
MLA
Touge, H., Chikumi, H., Igishi, T., Kurai, J., Makino, H., Tamura, Y., Takata, M., Yoneda, K., Nakamoto, M., Suyama, H., Gutkind, J. S., Shimizu, E."Diverse activation states of RhoA in human lung cancer cells: Contribution of G protein coupled receptors". International Journal of Oncology 30.3 (2007): 709-715.
Chicago
Touge, H., Chikumi, H., Igishi, T., Kurai, J., Makino, H., Tamura, Y., Takata, M., Yoneda, K., Nakamoto, M., Suyama, H., Gutkind, J. S., Shimizu, E."Diverse activation states of RhoA in human lung cancer cells: Contribution of G protein coupled receptors". International Journal of Oncology 30, no. 3 (2007): 709-715. https://doi.org/10.3892/ijo.30.3.709