title: Up-regulation of Bcl-2 by CD147 Through ERK Activation Results in Abnormal Cell Survival in Human Endometriosis.
abstract: BACKGROUND
  Human endometriosis (EMS) is characterized by insufficient apoptosis. Our previous studies have shown elevated CD147 expression in human endometriotic tissues and its involvement in endometrial cell apoptosis. However, the exact underlying mechanism remains elusive.
  
  
  OBJECTIVE
  The objective was to examine the correlation of the highly expressed CD147 with anti-apoptotic factor Bcl-2 in human endometriotic tissues and to determine the CD147-regulated apoptotic pathway in human endometrial epithelial cell line (HES).
  
  
  METHODS
  This was a laboratory study using human tissue analysis and HES cell culture.
  
  
  METHODS
  The setting was an academic research center and hospital.
  
  
  METHODS
  Patients were 30 women with ovarian EMS and 12 women without EMS.
  
  
  METHODS
  mRNA levels of CD147 and Bcl-2 were evaluated in endometriotic tissues by quantitative real-time PCR. HES cells were transfected with pcDNA3.0-CD147 overexpressing plasmid or immune-depleted by CD147 antibody.
  
  
  METHODS
  Main outcome measures were reverse transcription, quantitative real-time PCR, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, and Western blotting.
  
  
  RESULTS
  In human endometriotic tissues, Bcl-2 was up-regulated and positively correlated with CD147 expression, accompanied by activated ERK signaling. In HES cells, overexpression of CD147 increased viable cells and up-regulated Bcl-2 expression by activation of ERK signaling. Interference with CD147 function suppressed ERK signaling and decreased Bcl-2 expression, followed by accumulation of apoptotic factors, including cleaved caspase-9, cleaved caspase-3, and cleaved poly ADP-ribose polymerase.
  
  
  CONCLUSIONS
  The presently found strong correlations between Bcl-2 and CD147, ERK, and CD147 in human endometriotic lesions and the demonstrated reduced cell apoptosis through CD147-ERK-Bcl-2 intrinsic apoptosis signaling axis suggest that this CD147-regulated signaling may contribute to the enhanced cell survival in the progression of human EMS.
authors.affiliation: Epithelial Cell Biology Research Center (C.W., W.H., L.L.T., H.C., H.C.C.), Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Gynaecology (A.J., Z.C., X.Z., H.C.), The Second People's Hospital of Shenzhen, Shenzhen 518029, the People's Republic of China; and School of Biomedical Sciences Core Laboratory (H.C.C.), Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Epithelial Cell Biology Research Center (C.W., W.H., L.L.T., H.C., H.C.C.), Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Gynaecology (A.J., Z.C., X.Z., H.C.), The Second People's Hospital of Shenzhen, Shenzhen 518029, the People's Republic of China; and School of Biomedical Sciences Core Laboratory (H.C.C.), Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Aihong
authors.initials: A
authors.lastname: Jin
authors.affiliation: Epithelial Cell Biology Research Center (C.W., W.H., L.L.T., H.C., H.C.C.), Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Gynaecology (A.J., Z.C., X.Z., H.C.), The Second People's Hospital of Shenzhen, Shenzhen 518029, the People's Republic of China; and School of Biomedical Sciences Core Laboratory (H.C.C.), Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Huang
authors.affiliation: Epithelial Cell Biology Research Center (C.W., W.H., L.L.T., H.C., H.C.C.), Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Gynaecology (A.J., Z.C., X.Z., H.C.), The Second People's Hospital of Shenzhen, Shenzhen 518029, the People's Republic of China; and School of Biomedical Sciences Core Laboratory (H.C.C.), Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Lai Ling
authors.initials: LL
authors.lastname: Tsang
authors.affiliation: Epithelial Cell Biology Research Center (C.W., W.H., L.L.T., H.C., H.C.C.), Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Gynaecology (A.J., Z.C., X.Z., H.C.), The Second People's Hospital of Shenzhen, Shenzhen 518029, the People's Republic of China; and School of Biomedical Sciences Core Laboratory (H.C.C.), Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Epithelial Cell Biology Research Center (C.W., W.H., L.L.T., H.C., H.C.C.), Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Gynaecology (A.J., Z.C., X.Z., H.C.), The Second People's Hospital of Shenzhen, Shenzhen 518029, the People's Republic of China; and School of Biomedical Sciences Core Laboratory (H.C.C.), Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Xiaping
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Epithelial Cell Biology Research Center (C.W., W.H., L.L.T., H.C., H.C.C.), Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Gynaecology (A.J., Z.C., X.Z., H.C.), The Second People's Hospital of Shenzhen, Shenzhen 518029, the People's Republic of China; and School of Biomedical Sciences Core Laboratory (H.C.C.), Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Epithelial Cell Biology Research Center (C.W., W.H., L.L.T., H.C., H.C.C.), Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; Department of Gynaecology (A.J., Z.C., X.Z., H.C.), The Second People's Hospital of Shenzhen, Shenzhen 518029, the People's Republic of China; and School of Biomedical Sciences Core Laboratory (H.C.C.), Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000328:Adult; D051926:Basigin / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008875:Middle Aged; D010049:Ovarian Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C497886:BSG protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051926:Basigin