Tohoku J. Exp. Med., 2008, 216(2)

Growth Inhibitory Effect of the Ternary Complex Factor Net on Human Pancreatic Carcinoma Cell Lines

BAIWEN LI,¹ PEIHUA NI,² QI ZHU,¹ HAIXIA CAO,¹ HONG XU,³ SU ZHANG,¹ CHRIS AU⁴ and YONGPING ZHANG¹

¹Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China
²Faculty of Medicine laboratory science, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China
³Research Center for Human Gene Therapy, Department of Biochemistry Molecular Biology, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China
⁴School of Nursing and Midwifery, Victoria University, Melbourne, Australia

Pancreatic carcinoma is one of the most aggressive malignancies and carries the most dismal prognoses of all cancers. A better understanding of the genes involving in tumor development may allow us to tackle this rapidly progressive disease. The Net gene belongs to the ternary complex transcription factor (TCF) family and is regulated by the Ras/mitogen-activited protein kinase-signaling pathway. Under basal conditions, Net shows strong represssing function on transcription of proto-oncogene gene c-fos. Moreover, the lower expression of Net has been noted in some carcinoma cells, such as cervical cancer. To study the effect of Net on c-fos expression and its potential role in the growth of pancreatic carcinoma, we developed a recombinant plasmid, a pEGFP-N1-Net, which codes for Net-EGFP fusion proteins, and stably transfected it into BxPC-3 human pancreatic carcinoma cells. Using stable transformants, we were able to show that overexpression of Net decreased the expression of c-fos and inhibited pancreatic cancer cell proliferation. Cell cycle analysis demonstrated that Net overexpression inhibited cell cycle progression. These findings suggested that loss of Net repression could augment c-fos expression and further trigger neoplastic cell proliferation, which was involved in the pathogenesis of pancreatic cancer. Therefore, Net might be a potential target for the treatment of c-fos-positive pancreatic cancer.

keywords —— Net; c-fos; Proliferation; pancreatic carcinoma; cell cycle.

© 2008 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2008, 216, 139-147

Correspondence: Qi Zhu, M.D., PhD., Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.

e-mail: zhuqi@medmail.com.cn