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Protein kinase Cα promotes apoptotic cell death in gastric cancer cells depending upon loss of anchorage

Oncogene volume 18, pages 5604–5609 (1999)Cite this article

Abstract

Disruption of interactions between epithelial cells and extracellular matrix proteins leads to apoptosis of the cells, a phenomenon termed anoikis. Anoikis seems to play important roles in control of cellular positioning and inhibition of inappropriate cell growth. Here we found that a protein kinase C (PKC) activator phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) promoted cell death in human gastric cancer cell lines MKN45 and MKN74 only when they lost anchorage. Loss of anchorage slightly increased enzymatic activity of PKCα, and an addition of TPA promoted cell death with further increase of PKCα activity, but not PKCβ in MKN45 cells, implicating an involvement of PKCα in anoikis. Furthermore, vaccinia virus-mediated overexpression of PKCα strongly increased CPP32 activity in the detached MKN45 and MKN74 cells, and augmented anoikis, however it had little effect on viability and CPP32 activity in the attached cells. Taken together, PKCα promotes apoptotic cell death in gastric cancer cells depending upon loss of anchorage, thereby may be a modulator of anoikis.

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Acknowledgements

We thank Dr Yoshitaka Ono (Department of Biology, Faculty of Science, Kobe University) for providing PKCα cDNA. This work is supported by Grants-in-Aid for Scientific Research on Priority Area Cancer from the Ministry of Health and Welfare (K Imai and M Adachi), Japan.

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Authors and Affiliations

  1. The First Department of Internal Medicine, Sapporo Medical University School of Medicine, S1 W16, Chuo-Ku, Sapporo, 060-8543, Japan

    Hiroyuki Okuda, Masaaki Adachi, Yuji Hinoda & Kohzoh Imai

  2. Department of Immunology, Kinki University School of Medicine, 377-2, Ohhno-Higashi, Osaka-Sayama, 589, Osaka, Japan

    Masaaki Miyazawa

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  1. Hiroyuki Okuda
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Okuda, H., Adachi, M., Miyazawa, M. et al. Protein kinase Cα promotes apoptotic cell death in gastric cancer cells depending upon loss of anchorage. Oncogene 18, 5604–5609 (1999). https://doi.org/10.1038/sj.onc.1202946

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