title: In vivo inhibition of bone morphogenetic protein-2 on breast cancer cell growth.
abstract: METHODS
  In vitro and in vivo study.
  
  
  OBJECTIVE
  To evaluate the role of recombinant human bone morphogenetic protein-2 (rhBMP2) on breast cancer cell (MDA-MB-231 cells) growth.
  
  
  BACKGROUND
  Bone morphogenetic proteins (BMPs) are expressed in a variety of human carcinoma cell lines and are known to promote tumor invasion and metastasis. However, their roles in tumor progression have not been fully clarified. In addition, there is no in vivo study regarding the inhibitory effect of BMP2 on breast cancer cell proliferation.
  
  
  METHODS
  Cell proliferation was determined by BrdU incorporation assay and flow cytometry. BMP2 signal transduction pathways were estimated on Western blot. Fifteen animals were divided into 2 groups; 1 (control = 5) was breast cancer cells alone, while the other (experiment = 5) was rhBMP2 + breast cancer cells. Cancer cells were injected into 2 sites (subcutaneous and femur) of nude mice with or without BMP2. Tumor size was determined by direct measurements for subcutaneous tumor formation and by femur radiographs. Histological and immunohistochemical analyses were performed.
  
  
  RESULTS
  RhBMP2 inhibited the proliferation of MDA-MB-231 cells in vitro. Inhibition was associated with changes in both the Smad and Wnt signaling pathways and was ultimately mediated through effects on various cell cycle proteins. Furthermore, rhBMP2 inhibited the growth of MDA-MB-231 cells injected both subcutaneously and intrafemorally.
  
  
  CONCLUSIONS
  In this model using human breast adenocarcinoma cell line, rhBMP2 has no stimulatory effect of tumor growth. Therefore, we can provide the basic science data to support the utilization in the management of patients with spine tumor in the future.
authors.affiliation: Departments of Orthopaedic Surgery, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Shuai
authors.initials: S
authors.lastname: Ye
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Song
authors.forename: Jung-Ryul
authors.initials: JR
authors.lastname: Kim
authors.forename: Kyu-Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Ho-Sung
authors.initials: HS
authors.lastname: Park
authors.forename: Jun Sang
authors.initials: JS
authors.lastname: Bae
authors.forename: Elsa J
authors.initials: EJ
authors.lastname: Brochmann
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Murray
authors.forename: Kwang-Bok
authors.initials: KB
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011994:Recombinant Proteins / Q000494:pharmacology; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D055396:Bone Morphogenetic Protein 2; D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2