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Carcinogenesis Advance Access published online on May 13, 2008
Carcinogenesis, doi:10.1093/carcin/bgn112
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Pancreatic-duodenal homeobox 1 (PDX1) functions as a tumor suppressor in gastric cancer

Juan Ma1,2, Min Hu Chen1, Jide Wang2, Harry H. X. Xia2, Sen Lin Zhu1, Yingjie Liang3, Qing Gu2, Liang Qiao2, Yun Dai2, Bing Zou2, Zesong Li2, Yusheng Zhang2, Hui Yao Lan2 and Benjamin C.Y. Wong2,*

1 Division of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
2 Department of Medicine, University of Hong Kong, Hong Kong
3 Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

* Corresponding Author:Professor Benjamin C.Y. Wong, MD, PhD, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, Tel: 852 2855 5995, Fax: 852 2904 9443, Email: bcywong{at}hku.hk

Background & Aims: Pancreatic-duodenal homeobox 1(PDX1) is a transcription factor of homeobox genes family important in differentiation and development of the pancreas, duodenum and antrum. This study aims to clarify the putative role of PDX1 in gastric carcinogenesis.

Methods: PDX1 expression was detected in gastric tissues with chronic gastritis and cancer as well as gastric cancer cell lines by immunohistochemistry, western blot, RT-PCR or quantitative real-time RT-PCR assays. The effects of PDX1 on cell proliferation, apoptosis, clone formation, and migration were evaluated using cancer cell lines after transient or stable transfection with PDX1 expressing vector. The ability of PDX1 stable transfectant in tumor formation in xenograft mice was assessed.

Results: PDX1 was strongly expressed in normal gastric glands, but was absent in 29/39 of human gastric cancer and most gastric cancer cell lines. Negative correlation between PDX1 and Ki-67 expression was found in both gastric tissues and cell lines. Ectopic overexpression of PDX1 significantly inhibited cell proliferation and induced apoptosis, accompanied by the activation of caspase-3, -8, -9, and -10. Over-expression of PDX1 also impaired the ability of cancer cells in clonal formation and migration in vitro. Furthermore, stable transfection with PDX1 reduced the ability of cancer cells in tumor formation in nude mice.

Conclusions: PDX1 expression is lost in gastric cancers. Its effect on cell proliferation/apoptosis, migration and tumor formation in vitro and in vivo suggested that this protein functions as a putative tumor suppressor in gastric cancer.

Key Words: Pancreatic-duodenal homeobox 1 • gastric cancer • tumor suppressor

Received December 17, 2007; revised April 7, 2008; accepted April 28, 2008.


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