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

Abstract

Aim: 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, reverse transcription-polymerase chain reaction (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 of 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 caspases 3, 8, 9 and 10. Overexpression 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. © The Author 2008. Published by Oxford University Press. All rights reserved.