title: KLF15 in breast cancer: a novel tumor suppressor?
abstract: OBJECTIVE
  Krüppel-like factor 15 (KLF15) is a transcription factor that is involved in various biological processes, including cellular proliferation, differentiation and death. In addition, KLF15 has recently been implicated in the development of several human malignancies, including breast cancer. In vitro breast cancer studies have pointed at a putative role in the regulation of cell proliferation. As yet, however, KLF15 expression analyses in primary human breast cancers have not been reported. Here, we set out to investigate the clinical and biological significance of KLF15 expression in human breast cancers.
  
  
  METHODS
  KLF15 expression was evaluated by immunohistochemistry in 54 primary invasive ductal breast carcinomas, and its status was correlated with various clinicopathological parameters. We also assessed KLF15 expression in vitro in 4 breast cancer-derived cell lines using Western blotting, and examined the effects of exogenous KLF15 expression on cell cycle progression using flow cytometry. Concomitant (changes in) p21, p27 and TOPO2A expression levels were examined using real-time RT-PCR and immunocytochemistry, respectively.
  
  
  RESULTS
  In ~90% of the primary breast carcinoma tissues tested, KLF15 was found to be expressed and localized in either the cytoplasm, the nucleus or both. Predominant nuclear immunoreactivity was found to be associated with clinicopathological factors predicting a better clinical outcome (i.e., ER positive, HER2 negative, low grade, low Ki-67 expression). The breast cancer-derived cell lines tested showed a low KLF15 expression with a predominant cytoplasmic localization. Subsequent exogenous KLF15 over-expression resulted in a predominant nuclear localization and a concomitant decreased cellular proliferation and an arrest at the G0/G1 phase of the cell cycle. In addition, we found that nuclear KLF15 expression results in up-regulation of p21, a pivotal suppressor of the G1 to S phase transition of the cell cycle.
  
  
  CONCLUSIONS
  Our results indicate that nuclear KLF15 expression suppresses breast cancer cell proliferation at least partially through p21 up-regulation and subsequent cell cycle arrest. This is a first study addressing the role of KLF15 in breast cancer development.
authors: Departments of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors: Tomomi
authors: T
authors: Yoda
authors: Keely May
authors: KM
authors: McNamara
authors: Yasuhiro
authors: Y
authors: Miki
authors: Yoshiaki
authors: Y
authors: Onodera
authors: Kiyoshi
authors: K
authors: Takagi
authors: Yasuhiro
authors: Y
authors: Nakamura
authors: Takanori
authors: T
authors: Ishida
authors: Takashi
authors: T
authors: Suzuki
authors: Noriaki
authors: N
authors: Ohuchi
authors: Hironobu
authors: H
authors: Sasano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: C414172:KLF15 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins