Abstract
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.
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Acknowledgments
This work received support from INSERM. The authors wish to thank Ms Sylvie PICHET from the NOVARTIS laboratory for her support, and Ms Deborah Garcia for her efficient assistance in the organization of the reagents supply. The authors thank Dr. Laurent LAPLAZE for access to the DMRB microscope and images recording and Miss Joana TAVARES for the Western blot image analysis. We are indebted to Ms M. RADAL for her technical assistance in the preparation of cryosections of tissue samples. Dr. Leal Silvestre received a fellowship from the Fundação para a Ciência e Tecnologia (FCT) Portugal. Dr. Mehdi Ouaïssi was supported by Assistance Pubique-Hôpitaux de Marseille and University of Aix Marseille and has received a grant from the NOVARTIS Laboratory.
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Ouaïssi, M., Sielezneff, I., Silvestre, R. et al. High Histone Deacetylase 7 (HDAC7) Expression Is Significantly Associated with Adenocarcinomas of the Pancreas. Ann Surg Oncol 15, 2318–2328 (2008). https://doi.org/10.1245/s10434-008-9940-z
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DOI: https://doi.org/10.1245/s10434-008-9940-z