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Acetylation as a Transcriptional Control Mechanism—HDACs and HATs in Pancreatic Ductal Adenocarcinoma

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Abstract

Introduction

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.

Conclusion

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.

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Acknowledgments

The authors are supported by Deutsche Forschungsgemeinschaft (Grant SCHN 959/1-2), SFB456, SFB824, Else Kröner-Fresenius-Stiftung, Novartis-Stiftung für therapeutische Forschung, Fritz-Thyssen Stiftung, Bayerische Forschungsstiftung, and Deutsche Krebshilfe. We would like to apologize for not citing any relevant reports due to lack of space, the need to selectively choose examples, or an oversight on our part.

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  1. Klinikum rechts der Isar, II. Medizinische Klinik, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany

    Günter Schneider, Roland M. Schmid & Dieter Saur

  2. Center for Molecular Biomedicine, Institute of Biochemistry and Biophysics, Friedrich-Schiller-University Jena, Hans-Knöll-Str. 2, 07745, Jena, Germany

    Oliver H. Krämer

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  1. Günter Schneider
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Correspondence to Günter Schneider.

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Schneider, G., Krämer, O.H., Schmid, R.M. et al. Acetylation as a Transcriptional Control Mechanism—HDACs and HATs in Pancreatic Ductal Adenocarcinoma. J Gastrointest Canc 42, 85–92 (2011). https://doi.org/10.1007/s12029-011-9257-1

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