PAX6 is expressed in pancreatic adenocarcinoma and is downregulated during induction of terminal differentiation
PAX6 is expressed in pancreatic adenocarcinoma and is downregulated during induction of terminal differentiation
复制标题
DOI：
10.1002/mc.20375
复制
发表时间：
2008-02-01
影响因子：
4.6
通讯作者：
Ruggeri, Bruce A.
中科院分区：
文献类型：
--
作者：
Lang, Deborah;Mascarenhas, Joseph B.;Ruggeri, Bruce A.
胰腺外分泌肿瘤是癌症死亡的主要原因，并且在所有恶性肿瘤中预后最差。根据“癌症干细胞假说”，即肿瘤被认为起源于组织特异性干细胞，我们筛选了原发性胰腺导管癌和细胞系，以表达可能的干细胞因子。我们发现32/46（70%）的原发性肿瘤和9/10（90%）的细胞系表达PAX 6。PAX 6是一种转录因子，在胚胎发育过程中在整个胰腺芽中表达，但在成熟的外分泌胰腺中不表达。PAX蛋白还涉及维持干细胞处于定向但未分化状态，但PAX蛋白在推定的胰腺干细胞中的作用尚不清楚。我们诱导胰腺癌细胞系Panc-1，通过去除野生型p53和用分化剂胃泌素或丁酸盐处理细胞来分化。这种处理诱导细胞终末分化为具有神经突样突起的生长停滞细胞，表达终末分化标志物生长抑素并下调PAX 6。这种表型可以通过直接抑制PAX 6表达来复制。这些数据支持PAX蛋白在肿瘤中异常表达并且下调导致分化的模型。(C)2007 Wiley-Liss，Inc.
Tumors of the exocrine pancreas are a major cause of cancer death and have among the poorest prognosis of any malignancy. Following the "cancer stem cell hypothesis," where tumors are believed to originate in tissue specific stem cells, we screened primary ductal pancreatic carcinomas and cell lines for the expression of possible stem cell factors. We find 32/46 (70%) of primary tumors and 9/10 (90%) of cell lines express PAX6. PAX6 is a transcription factor expressed throughout the pancreatic bud during embryogenesis but not in the mature exocrine pancreas. PAX proteins have also been implicated in maintaining stem cells in a committed but undifferentiated state but a role for PAX proteins in putative pancreas stem cells is not known. We induced a pancreatic carcinoma cell line, Panc-1, to differentiate by transfecting wild-type p53 and treating the cells with differentiation agents gastrin or butyrate. This treatment induces cells to terminally differentiate into a growth-arrested cell with neurite-like processes, express the terminal differentiation marker somatostatin and downregulate PAX6. This phenotype can be replicated by directly inhibiting PAX6 expression. These data support a model where PAX proteins are aberrantly expressed in tumors and downregulation leads to differentiation. (C) 2007 Wiley-Liss, Inc.