Ouaïssi Mehdi, Sielezneff Igor, Silvestre Ricardo, Sastre Bernard, Bernard Jean-Paul, Lafontaine Joelle Simony, Payan Marie José, Dahan Laetitia, Pirrò Nicolas, Seitz Jean François, Mas Eric, Lombardo Dominique, Ouaissi Ali
Service de Chirurgie Digestive et Oncologique, Pôle d'Oncologie et Spécialité Médico-Chirurgicales, Assistance Pubique-Hôpitaux de Marseille, Hôpital Timone, 264 Rue Saint Pierre, Marseille 13000, France.
Ann Surg Oncol. 2008 Aug;15(8):2318-28. doi: 10.1245/s10434-008-9940-z. Epub 2008 May 28.
Alterations in HDACs gene expression have been reported in a number of human cancers. No information is available concerning the status of HDACs in pancreatic cancer tumors. The aim of the present study was to evaluate the expression levels of members of class I (HDAC1, 2,, 3), class II (HDAC4, 5, 6, and 7), and class III (SIRT1, 2, 3, 4, 5, and 6) in a set of surgically resected pancreatic tissues.
Total RNA was isolated from 11 pancreatic adenocarcinomas (PA): stage 0 (n = 1), IB (n = 1), IIB (n = 6), III (n = 1), IV (n = 2), one serous cystadenoma (SC), one intraductal papillary mucinous tumor of the pancreas (IMPN), one complicating chronic pancreatitis (CP), and normal pancreas (NP) obtained during donor liver transplantation. Moreover, six other control pancreatic were included. HDACs gene expression was conducted using quantitative real-time polymerase chain reaction (qPCR). Protein expression levels were analyzed by Western blot and their localization by immunohistochemistry analyses of cancer tissues sections.
Remarkably, 9 of the 11 PA (approximately 81%) showed significant increase of HDAC7 mRNA levels. In contrast to PA samples, message for HDAC7 was reduced in CP, SC, and IMPN specimens. The Western blot analysis showed increased expression of HDAC7 protein in 9 out of 11 PA samples, in agreement with the qPCR data. Most of the PA tissue sections examined showed intense labeling in the cytoplasm when reacted against antibodies to HDAC7.
The data showed alteration of HDACs gene expression in pancreatic cancer. Increased expression of HDAC7 discriminates PA from other pancreatic tumors.
已有报道称多种人类癌症中存在组蛋白去乙酰化酶（HDACs）基因表达改变。关于胰腺癌肿瘤中HDACs的状态尚无相关信息。本研究的目的是评估一组手术切除的胰腺组织中I类（HDAC1、2、3）、II类（HDAC4、5、6和7）和III类（SIRT1、2、3、4、5和6）成员的表达水平。
从11例胰腺腺癌（PA）中分离总RNA：0期（n = 1）、IB期（n = 1）、IIB期（n = 6）、III期（n = 1）、IV期（n = 2），1例浆液性囊腺瘤（SC），1例胰腺导管内乳头状黏液性肿瘤（IMPN），1例合并慢性胰腺炎（CP）以及供体肝移植时获取的正常胰腺（NP）。此外，还纳入了另外6个对照胰腺组织。使用定量实时聚合酶链反应（qPCR）进行HDACs基因表达检测。通过蛋白质印迹分析蛋白质表达水平，并通过对癌组织切片进行免疫组织化学分析确定其定位。
值得注意的是，11例PA中有9例（约81%）显示HDAC7 mRNA水平显著升高。与PA样本相反，HDAC7在CP、SC和IMPN标本中的表达降低。蛋白质印迹分析显示，11例PA样本中有9例HDAC7蛋白表达增加，与qPCR数据一致。大多数检测的PA组织切片与HDAC7抗体反应时，在细胞质中显示强烈染色。
数据显示胰腺癌中HDACs基因表达发生改变。HDAC7表达增加可将PA与其他胰腺肿瘤区分开来。
