Experimental Therapeutics

British Journal of Cancer (2003) 88, 606–612. doi:10.1038/sj.bjc.6600739 www.bjcancer.com
Published online 18 February 2003

Gelsolin suppresses tumorigenicity through inhibiting PKC activation in a human lung cancer cell line, PC10

N Sagawa1,2, H Fujita1, Y Banno3, Y Nozawa4, H Katoh2 and N Kuzumaki1

  1. 1Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, N15 W7 Kita-ku, Sapporo 060-0815, Japan
  2. 2Surgical Oncology, Cancer Medicine, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
  3. 3Department of Biochemistry, Gifu University School of Medicine, Tsukasamachi-40, Gifu 500-8706, Japan
  4. 4Department of Environmental Cell Responses, Gifu International Institute of Biotechnology and Institute of Applied Biochemistry, Mitake, Gifu 505-0116, Japan

Correspondence: Dr H Fujita, E-mail: h_fujita@med.hokudai.ac.jp

Received 5 June 2002; Revised 14 October 2002; Accepted 31 October 2002.

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Abstract

Gelsolin expression is frequently downregulated in lung cancer and several types of different human cancers. To examine the effects of gelsolin restoration on tumorigenicity, we here stably expressed various levels of gelsolin via gene transfer in lung cancer cells (squamous cell carcinoma line, PC10). We observed the alterations in tumorigenicity in vivo when implanted in nude mice, and the changes in growth properties in vitro. As compared to parental cells and control clones, gelsolin transfectants highly reduced tumorigenicity and repressed cell proliferation. Moreover, we investigated bradykinin-induced responses in gelsolin-overexpressing clones, because agonist-stimulated activation of the phospholipases C (PLC)/protein kinase C (PKC) signal transduction pathway is critical for cell growth and tumorigenicity. Bradykinin promotes phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis by PLC and translocation of various PKC isoforms from the cytosolic fraction to the particulate fraction. Bradykinin treatment did not increase inositoltriphosphate (IP3) production and induce the membrane fractions of PKCalpha and PKCitalic gamma in gelsolin tranfectants, while it induced PIP2 hydrolysis and increased the fractions in parental and control clones. These results suggest that gelsolin suppressed the activation of PKCs involved in phospholipid signalling pathways, inhibiting cell proliferation and tumorigenicity.

Keywords:

gelsolin, phosphoinositides, PKC, lung cancer, tumour suppression