Screening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class I HDAC profiles between epithelial and stromal cells.
Histone deacetylases (HDACs) represent a large family of enzymes identified as key regulators of nucleosomal histone acetylation, a major epigenetic event that controls eukaryotic gene transcription. Inappropriate deacetylation mediated by HDACs has been associated with profound alterations in cellular biology. We have thus hypothesized that an altered HDAC expression may favor cancer development/progression. To test this possibility, we have sought to screen the expression profiles of several class I and class II HDACs (HDAC1-8) in DU-145, PC-3 and LNCaP human prostate cancer cell lines as well as in matched malignant and non-malignant prostate tissues by use of real time RT-PCR, immunoblot and immunohistochemistry. All HDAC transcripts tested were detected at various levels in all prostate cancer cell lines and tissue samples analyzed. In prostate tissues, the abundance of HDAC1 protein, which was exclusively expressed in the cell nucleus, was similar in normal and malignant epithelial cells, but was usually lower in stromal cells. Unexpectedly, HDAC8, another class I HDAC, was not detected in epithelial cells but was uniquely expressed in the cytoplasm of stromal cells. HDAC5, a class II HDAC involved in myogenesis, was not detected in the tissues. Altogether, our findings indicate that epithelial and stromal cells exhibit distinct class I HDAC expression profiles, and the abundance of HDAC1 is not altered in human prostate cancer. In addition, our observations are the first to demonstrate the prominently cytosolic distribution of a class I HDAC, HDAC8.
Waltregny
D
D
Metastasis Research Laboratory, Pathology Building, Bat. B23, level -1, CHU Sart Tilman Liège, B-4000 Liège 1, Belgium. david.waltregny@ulg.ac.be
North
B
B
Van Mellaert
F
F
de Leval
J
J
Verdin
E
E
Castronovo
V
V
D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000201:enzymology*; D005455:Fluorescent Antibody Technique / Q000379:methods; D005820:Genetic Testing; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000032:analysis / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics; D017154:Stromal Cells / Q000201:enzymology*
D012097:Repressor Proteins; C110550:HDAC1 protein, human; C404500:HDAC5 protein, human; C409470:HDAC8 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases