Homeobox gene CDX2 inhibits human pancreatic cancer cell proliferation by down-regulating cyclin D1 transcriptional activity.
OBJECTIVE
Homeobox gene caudal related homeobox gene 2 (CDX2) is an intestine-specific tumor suppressor gene. This study is intended to investigate the effect of CDX2 expression on cell proliferation and cyclin D1 expression in pancreatic cancer cells.


METHODS
Four pancreatic ductal adenocarcinoma cell lines (PancQGO-1, BxPC-3, MIAPaCa-2, CFPAC-1), 1 islet carcinoma cell line (QGP-1), and 1 adenosquamous carcinoma cell line (KP-3) were analyzed for CDX1 and CDX2 expression using real-time reverse transcription-polymerase chain reaction and Western blot analysis. Proliferation of pancreatic cancer cells was analyzed using WST-1 assay after CDX2 transfection. Luciferase assay was performed to examine the effects of CDX2 on cyclin D1 transcriptional activity.


RESULTS
CDX2 was expressed at a significantly higher level in QGP-1 cells than in KP-3 cells. Moreover, CDX2 was expressed at a middle level in 4 pancreatic ductal adenocarcinoma cells. Cell proliferation and cyclin D1 mRNA level were inhibited significantly after CDX2 transfection in pancreatic cancer cells. Furthermore, CDX2 inhibited exogenous nuclear factor kappaB-p65-induced luciferase gene expression in a dose-dependent manner. In addition, CDX2 inhibited pGL2HIVD1kappaB2-luciferase activity.


CONCLUSIONS
CDX2 might play a role in inhibiting cell proliferation and repressing cyclin D1 transcriptional activity through the proximal nuclear factor kappaB binding site in pancreatic cancer cells.
Takahashi
Kenji
K
Division of Metabolism and Biosystemic Sciences, Department of Medicine, Asahikawa Medical College, Asahikawa, Japan. t-kenji@asahikawa-med.ac.jp
Hirano
Fuminori
F
Matsumoto
Kakuya
K
Aso
Kazunobu
K
Haneda
Masakazu
M
D000071616:CDX2 Transcription Factor; D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000473:pathology; D018273:Carcinoma, Islet Cell / Q000235:genetics / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
C530104:CCND1 protein, human; C491273:CDX1 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D019938:Cyclin D1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human