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10.1245/s10434-008-9940-z
Annals of Surgical Oncology 15:2318-2328 (2008)
© 2008 Society of Surgical Oncology
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Original Article

High Histone Deacetylase 7 (HDAC7) Expression Is Significantly Associated with Adenocarcinomas of the Pancreas

Mehdi Ouaïssi, MD1,2,3,4, Igor Sielezneff, MD1,2, Ricardo Silvestre, PhD4,5, Bernard Sastre, MD1,2, Jean-Paul Bernard, MD, PhD2,3, Joelle Simony Lafontaine, MD, PhD7, Marie José Payan, MD, PhD8, Laetitia Dahan, MD2,9, Nicolas Pirrò, MD1,2, Jean François Seitz, MD, PhD2,9, Eric Mas, PhD3, Dominique Lombardo, PhD3 and Ali Ouaissi, PhD4,5,6

1 Service de chirurgie digestive et oncologique, pôle d’oncologie et spé cialitémé dico-chirurgicales, Assistance Pubique-Hôpitaux de Marseille, Hôpital Timone, 264 Rue Saint Pierre, Marseille 13000, France
2 Facultéde Mé decine, Aix Marseille Université , Marseille 13000, France
3 INSERM, UMR911, Marseille 13000, France
4 IRD, UR008, Montpellier 34394, France
5 IBMC, Universidade do Porto, Porto 4150-180, Portugal
6 INSERM, CNRS UMR 5235, UniversitéMontpellier 2, Montpellier, France
7 Service d’Anathomopathologie, CRLC, Hôpital Val d’Aurel, Montpellier 34298, France
8 Service d’anathomopathologie, pôle d’oncologie et spé cialitémé dico-chirurgicales, Assistance Pubique-Hôpitaux de Marseille, Hôpital Timone, Marseille 13000, France
9 Service d’oncologie digestive, pôle d’oncologie et spé cialitémé dico-chirurgicales, Assistance Pubique-Hôpitaux de Marseille, Hôpital Timone, Marseille 13000, France

Correspondence: Address correspondence and reprint requests to: Mehdi Ouaïssi, MD; E-mail: mehdi.ouaissi{at}mail.ap-hm.fr

Background: 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.

Methods: 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.

Results: 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.

Conclusion: The data showed alteration of HDACs gene expression in pancreatic cancer. Increased expression of HDAC7 discriminates PA from other pancreatic tumors.

Key Words: Pancreatic tumors • HDACs • SIRTs • RT-PCR • qPCR • Gene expression







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