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Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells

Oncogene volume 27, pages 2810–2822 (2008)Cite this article

Abstract

Pancreatic cancer still remains one of the most lethal diseases and establishment of new therapy is needed. The purpose of this study is to find novel factors involved in pancreatic cancer progression by proteomic approach. We compared pre- and postoperative serum protein profiling obtained from pancreatic cancer patients who had curative pancreatectomy using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. The peak intensity levels of both 6630 and 6420 Da were significantly higher in the preoperative serum than in the postoperative serum (P<0.002). Sequential amino acid analysis identified these proteins to be apolipoprotein C-1 (ApoC-1). The high level of ApoC-1 in preoperative serum significantly correlated with poor prognosis. Furthermore, ApoC-1 was abundantly expressed in pancreas neoplastic epithelium, and was detected in the culture medium of the pancreatic cancer cell line in vitro, which suggests that cancer cells secrete ApoC-1. Inhibition of ApoC-1 expression by short interfering RNA suppressed cell proliferation and induced apoptosis of pancreatic cancer cells. The specific expression of ApoC-1 and its role in preventing from spontaneous apoptosis in pancreatic cancer cells suggest that ApoC-1 contributes to the aggressiveness of pancreatic cancer and will be useful as a new therapeutic target.

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Acknowledgements

This study was supported by the Ministry of Education, Culture, Science, Sports and Technology of Japan and Japanese Society of Laboratory Medicine Fund for Promotion of Scientific Research (2006–2007). We thank Mamoru Satoh, PhD and Masumi Ishibashi for technical support and Kosuke Suda, MD, PhD and Kazuki Kobayashi, MD, PhD for special advice.

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Authors and Affiliations

  1. Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

    S Takano, H Yoshitomi, A Togawa, T Shida, F Kimura, H Shimizu & M Miyazaki

  2. Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan

    S Takano, K Sogawa, T Tomonaga & F Nomura

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  1. S Takano
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  2. H Yoshitomi
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  3. A Togawa
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  7. H Shimizu
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  8. T Tomonaga
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  9. F Nomura
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  10. M Miyazaki
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Correspondence to H Yoshitomi.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Takano, S., Yoshitomi, H., Togawa, A. et al. Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells. Oncogene 27, 2810–2822 (2008). https://doi.org/10.1038/sj.onc.1210951

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