title: Up-regulated p27Kip1 reduces matrix metalloproteinase-9 and inhibits invasion of human breast cancer cells.
abstract: BACKGROUND
  p27Kip1 is a cyclin-dependent kinase inhibitor which has been reported to be associated with invasion, metastasis and angiogenesis in malignant tumors, but its mechanism of action remains unknown. Here, it was examined whether p27Kip1 has an inhibitory effect on cancer cell invasion and correlates with matrix metalloproteinase expression (MMPs).
  
  
  METHODS
  The human breast cancer cell line MDA-MB-231 and MDA-MB-231 transfectedp27Kip1 MDA-MB-p27 were used for the invasion assay, Western blotting and real-time quantitative RT-PCR.
  
  
  RESULTS
  In the invasion assay, the invasion of MDA-MB-p27 was significantly less than that of the parent cell line. In Western blotting analyses, the protein level of MMP-9 was also reduced in MDA-MB-p27. Furthermore, the activity of MMP-9 in cell culture supernatants was lower in MDA-MB-p27 as compared with enzyme-linked immunosorbent assays. In real-time quantitative RT-PCR, the mRNA level of MMP-9 was lower in MDA-MB-p27 cells.
  
  
  CONCLUSIONS
  Up-regulation of p27Kip1 remarkably inhibited the invasion of the breast cancer cells, in part due to the reduced expression of MMP-9. This is the first report of p27Kip1 modulating MMP-9 and indicating that p27Kip1 might play a key role in tumor cell invasion.
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Mizuma
authors.forename: Yu
authors.initials: Y
authors.lastname: Katayose
authors.forename: Kuniharu
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Shiraso
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yabuuchi
authors.forename: Akira
authors.initials: A
authors.lastname: Oda
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Masuda
authors.forename: Toshiki
authors.initials: T
authors.lastname: Rikiyama
authors.forename: Tohru
authors.initials: T
authors.lastname: Onogawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Ohtsuka
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Motoi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Egawa
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
chemical_list: C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020780:Matrix Metalloproteinase 9