title: Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity.
abstract: BACKGROUND
  Loss of histone H4 lysine 20 trimethylation (H4K20me3) is associated with multiple cancers, but its role in breast tumors is unclear. In addition, the pathological effects of global reduction in H4K20me3 remain mostly unknown. Therefore, a major goal of this study was to elucidate the global H4K20me3 level in breast cancer tissue and investigate its pathological functions.
  
  
  METHODS
  Levels of H4K20me3 and an associated histone modification, H3 lysine 9 trimethylation (H3K9me3), were evaluated by immunohistochemistry in a series of breast cancer tissues. Univariate and multivariate clinicopathological and survival analyses were performed. We also examined the effect of overexpression or knockdown of the histone H4K20 methyltransferases, SUV420H1 and SUV420H2, on cancer-cell invasion activity in vitro.
  
  
  RESULTS
  H4K20me3, but not H3K9me3, was clearly reduced in breast cancer tissue. A reduced level of H4K20me3 was correlated with several aspects of clinicopathological status, including luminal subtypes, but not with HER2 expression. Multivariate analysis showed that reduced levels of H4K20me3 independently associated with lower disease-free survival. Moreover, ectopic expression of SUV420H1 and SUV420H2 in breast cancer cells suppressed cell invasiveness, whereas knockdown of SUV420H2 activated normal mammary epithelial-cell invasion in vitro.
  
  
  CONCLUSIONS
  H4K20me3 was reduced in cancerous regions of breast-tumor tissue, as in other types of tumor. Reduced H4K20me3 level can be used as an independent marker of poor prognosis in breast cancer patients. Most importantly, this study suggests that a reduced level of H4K20me3 increases the invasiveness of breast cancer cells in a HER2-independent manner.
authors: Yuhki
authors: Y
authors: Yokoyama
authors: Ayaka
authors: A
authors: Matsumoto
authors: Miki
authors: M
authors: Hieda
authors: Yoshimi
authors: Y
authors: Shinchi
authors: Eri
authors: E
authors: Ogihara
authors: Mai
authors: M
authors: Hamada
authors: Yu
authors: Y
authors: Nishioka
authors: Hiroshi
authors: H
authors: Kimura
authors: Katsuhide
authors: K
authors: Yoshidome
authors: Masahiko
authors: M
authors: Tsujimoto
authors: Nariaki
authors: N
authors: Matsuura
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis / Q000235:genetics; D006657:Histones / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008745:Methylation; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; C542918:KMT5C protein, human; C508053:ERBB2 protein, human