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Inactivation of ErbB3 by siRNA promotes apoptosis and attenuates growth and invasiveness of human lung adenocarcinoma cell line A549

Oncogene volume 24, pages 1847–1859 (2005)Cite this article

Abstract

The ErbB3 receptor and the downstream signaling kinase Akt are implicated in proliferation of lung adenocarcinoma cells. Inhibition by siRNAs to ErbB3 and Akt isoforms 1, 2 and 3 was utilized to investigate the contribution of these molecules to tumor survival, spreading and invasiveness, and the roles of specific Akt isoforms. ErbB3 siRNA stably and dose-dependently suppressed ErbB3 protein for 2 days or more, and reduced cell numbers, by both suppressing cell cycle and causing apoptosis and necrosis. It also inhibited soft agar growth, cell motility and migration, and invasiveness. Akt1, 2 and 3 siRNAs had similar suppressive effects on cell number, apoptosis/necrosis and soft agar growth. However, although Akt1 siRNA had no effect on cell migration or invasion, Akt2 siRNA effectively suppressed both activities, and Akt3 siRNA had moderate effectiveness. In A549 cells, ErbB3 is indicated as having major effects on cell division, survival, motility, migration and invasiveness. All three Akt isoforms are to varying degrees involved in these cell behaviors, with Akt2 especially implicated in migration and invasion. ErbB3 and the Akts are promising targets for therapy, and siRNAs may be useful for this purpose.

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Acknowledgements

We thank Refika B Turnier for flow cytometric analysis and Dr Keith Kikawa for critical comments on this manuscript. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This project has been funded in part with Federal funds from the National Cancer Institute under contract no. NO1-CO-12400.

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Authors and Affiliations

  1. Basic Research Program, SAIC Frederick, National Cancer Institute, Frederick, MD, 21702-1201, USA

    Gunamani Sithanandam & Laura W Fornwald

  2. Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD, 21702-1201, USA

    Janet Fields & Lucy M Anderson

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  1. Gunamani Sithanandam
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  2. Laura W Fornwald
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Correspondence to Gunamani Sithanandam.

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Sithanandam, G., Fornwald, L., Fields, J. et al. Inactivation of ErbB3 by siRNA promotes apoptosis and attenuates growth and invasiveness of human lung adenocarcinoma cell line A549. Oncogene 24, 1847–1859 (2005). https://doi.org/10.1038/sj.onc.1208381

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