Schneider Günter, Krämer Oliver H, Schmid Roland M, Saur Dieter
Klinikum rechts der Isar, II. Medizinische Klinik, Technische Universität München, Ismaninger Strasse 22, Munich, Germany.
J Gastrointest Cancer. 2011 Jun;42(2):85-92. doi: 10.1007/s12029-011-9257-1.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with a dismal prognosis. Although our understanding of the carcinogenesis of the disease increases continuously, no effective conservative therapeutic strategies exist. Therefore, novel targets have to be defined at the experimental level. Histone deacetylases (HDACs), especially the class I isoenzymes HDAC1, 2, and 3, are highly expressed in PDAC.
This article summarizes the expression and functions of HDAC isoenzymes in PDAC, with a special focus on their promoter-specific mode of action. Although we have gained some molecular insight into the HDAC function in PDAC, less is known about the relevance of histone acetyltransferases (HATs) in PDAC. As an example, we will summarize function of the HAT p300, for which promoter-specific functions were described recently. Increasing the molecular insights into the functions of the acetylating and deacetylating machineries in PDAC are important, since this will lead to novel rationally based therapeutic strategies in the future.
胰腺导管腺癌（PDAC）是预后极差的最恶性肿瘤之一。尽管我们对该疾病致癌作用的理解不断加深，但目前尚无有效的保守治疗策略。因此，必须在实验层面确定新的靶点。组蛋白去乙酰化酶（HDACs），尤其是I类同工酶HDAC1、2和3，在PDAC中高表达。
本文总结了HDAC同工酶在PDAC中的表达和功能，特别关注其启动子特异性作用模式。尽管我们对HDAC在PDAC中的功能有了一些分子层面的认识，但对组蛋白乙酰转移酶（HATs）在PDAC中的相关性了解较少。例如，我们将总结HAT p300的功能，最近已描述了其启动子特异性功能。深入了解PDAC中乙酰化和去乙酰化机制的功能在分子层面很重要，因为这将在未来带来基于合理依据的新治疗策略。
