Oct4 and Nanog expression is associated with early stages of pancreatic carcinogenesis.
OBJECTIVE
To characterize the role of Oct4 and Nanog, two important homeobox transcription factors of embryonic development, in pancreatic carcinogenesis.


METHODS
Using a tissue microarray of human pancreatic carcinoma and adjacent noncancerous tissues as well as the N-nitrosobis(2-oxopropyl)amine-induced Syrian golden hamster pancreatic cancer model, we characterized the expression of Oct4 and Nanog. The presence of K-ras mutation with the time course of carcinogenesis in hamster model was also evaluated.


RESULTS
Oct4 expression in metaplastic ducts was significantly stronger than in normal acini and pancreatic carcinoma (P < 0.05). Of 24 cases, 19 (79.2%) showed a strong Oct4 expression in metaplastic ducts. In contrast, only 6 (19.4%) of 31 cancer tissues and 3 (16.7%) of 18 noncancer tissues showed a strong Oct4 expression. Nanog also showed similar patterns as Oct4. Restriction fragment length polymorphism-polymerase chain reaction showed the overt K-ras mutation after the expression of Oct4 in the hamster model.


CONCLUSIONS
The strong expression of Oct4 and Nanog in metaplastic ducts and Oct4 expression preceding Ras mutation suggests that these homeobox transcription factors are associated with the early stage of pancreatic cancer carcinogenesis and may play an important role in that process.
Wen
Jing
J
Division of Gastroenterology, Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
Park
Jeong Youp
JY
Park
Kyung Hwa
KH
Chung
Hye Won
HW
Bang
Seungmin
S
Park
Seung Woo
SW
Song
Si Young
SY
D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D011905:Genes, ras; D018398:Homeodomain Proteins / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D009154:Mutation; D000071317:Nanog Homeobox Protein; D009602:Nitrosamines / Q000494:pharmacology; D050814:Octamer Transcription Factor-3 / Q000032:analysis / Q000096:biosynthesis*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D009602:Nitrosamines; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C013622:nitrosobis(2-oxopropyl)amine