Division of Gastroenterology, Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
Pancreas. 2010 Jul;39(5):622-6. doi: 10.1097/MPA.0b013e3181c75f5e.
To characterize the role of Oct4 and Nanog, two important homeobox transcription factors of embryonic development, in pancreatic carcinogenesis.
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.
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.
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.
研究胚胎发育过程中两个重要同源盒转录因子 Oct4 和 Nanog 在胰腺癌发生中的作用。
采用人胰腺癌组织及其相邻正常组织的组织微阵列以及 N-亚硝双(2-氧丙基)胺诱导的叙利亚金黄地鼠胰腺癌模型,对 Oct4 和 Nanog 的表达进行了研究。还评估了仓鼠模型中致癌过程中 K-ras 突变的存在。
化生导管中 Oct4 的表达明显强于正常腺泡和胰腺癌(P < 0.05)。在 24 例中,19 例(79.2%)的化生导管中 Oct4 表达较强。相比之下,只有 6 例(19.4%)的 31 例癌组织和 3 例(16.7%)的 18 例非癌组织中 Oct4 表达较强。Nanog 的表达模式与 Oct4 相似。在仓鼠模型中 Oct4 表达后,出现明显的 K-ras 突变。
化生导管中 Oct4 和 Nanog 的强表达以及 Oct4 表达先于 Ras 突变,提示这些同源盒转录因子与胰腺癌发生的早期阶段有关,可能在该过程中发挥重要作用。