title: METCAM/MUC18 promoted tumorigenesis of human breast cancer SK-BR-3 cells in a dosage-specific manner.
abstract: OBJECTIVE
  Overexpression of METCAM/MUC18, an immunoglobulin-like cell-adhesion molecule, promotes tumorigenesis and progression of human breast cancer cells. We also observed an intriguing phenomenon that a high-expressing SK-BR-3 clone manifested a transient tumor suppression effect in vivo. The purpose of this study was to understand if this was caused by clonal variation, METCAM/MUC18-dosage effect, or the number of cells injected.
  
  
  METHODS
  Several G418-resistant clones of SK-BR-3, expressing different levels of METCAM/MUC18, were obtained for testing effects of human METCAM/MUC18 on in vitro motility, invasiveness, and anchorage-independent colony formation (in vitro tumorigenicity) and in vivo tumorigenesis in female Balb/C athymic nude mice. Tumor sections were made for histology and immunohistochemistry analyses, and tumor lysates for Western blot analysis to determine the effects of human METCAM/MUC18 expression on levels of various downstream effectors.
  
  
  RESULTS
  METCAM/MUC18 promoted in vitro motility, invasiveness, and in vitro tumorigenicity of SK-BR-3 cells in a dosage-specific manner. Overexpression of METCAM/MUC18 could promote in vivo tumorigenesis of SK-BR-3 cells even when one tenth of the previously used cell number (5 × 10(5)) was injected and in vivo tumorigenesis of SK-BR-3 cells was directly proportional to the dosage of the protein. The previously observed transient tumor suppression effect from the same clone was no longer observed. The downstream effector, such as phospho-AKT/AKT ratio, was elevated in the tumors.
  
  
  CONCLUSIONS
  Transient suppression observed previously in the clone was caused by injection of a high cell number (2 × 10(6)-5 × 10(6)). METCAM/MUC18 positively promotes tumorigenesis of SK-BR-3 cells by increasing the survival and proliferation pathway.
authors.affiliation: Department of Bioscience Technology and Center for Biomedical Technology, Chung Yuan Christian University, Chung Li District, Taoyuan City 32023, Taiwan, ROC.
authors.forename: Chang-Yu
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Bioscience Technology and Center for Biomedical Technology, Chung Yuan Christian University, Chung Li District, Taoyuan City 32023, Taiwan, ROC; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: guangj.wu@gmail.com.
authors.forename: Guang-Jer
authors.initials: GJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051929:CD146 Antigen / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D002999:Clone Cells; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014410:Tumor Stem Cell Assay
chemical_list: D051929:CD146 Antigen; C497902:MCAM protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Balb/C athymic nude mice; METCAM/MUC18; SK-BR-3 cells; invasiveness & migration; tumorigenesis