title: Histone deacetylases 1, 6 and 8 are critical for invasion in breast cancer.
abstract: Histone deacetylases (HDACs) are associated with the development and progression of cancer, but it is not known which of the HDAC isoforms play important roles in breast cancer metastasis. This study identified the specific HDAC isoforms that are necessary for invasion and/or migration in human breast cancer cell lines. MDA-MB-231 cells were significantly more invasive and expressed higher levels of matrix metalloproteinase-9 (MMP-9) compared to MCF-7 cells. We compared the expression of HDAC isoforms between MCF-7 and MDA-MB-231 cells and found greater expression of HDAC4, 6 and 8 in MDA-MB-231 cells by RT-PCR and Western blot analyses. In addition, apicidin, a histone deacetylase inhibitor, was shown to attenuate the invasion, migration and MMP-9 expression in MDA-MB-231 cells. Using specific siRNAs directed against HDAC1, 4, 6 and 8, we show that inhibition of HDAC1, 6 and 8, but not HDAC4, are responsible for invasion and MMP-9 expression in MDA-MB-231 cells. We analyzed the invasiveness of MCF-7 cells overexpressing HDAC1, 4, 6 or 8 and found that overexpression of HDAC1, 6 or 8 increased invasion and MMP-9 expression. By developing HDAC isoforms as potential biomarkers for breast cancer metastasis, the present study can be extended to developing therapies for breast cancer invasion.
authors: Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors: Soon Young
authors: SY
authors: Park
authors: Ji Ae
authors: JA
authors: Jun
authors: Kang Jin
authors: KJ
authors: Jeong
authors: Hoi Jeong
authors: HJ
authors: Heo
authors: Jang Sihn
authors: JS
authors: Sohn
authors: Hoi Young
authors: HY
authors: Lee
authors: Chang Gyo
authors: CG
authors: Park
authors: Jaeku
authors: J
authors: Kang
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D056284:Histone Deacetylase 1 / Q000096:biosynthesis*; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000096:biosynthesis*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000473:pathology*; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D034741:RNA, Small Interfering; D012097:Repressor Proteins; D020780:Matrix Metalloproteinase 9; C433811:HDAC6 protein, human; C409470:HDAC8 protein, human; D056284:Histone Deacetylase 1; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases