title: Human epithelial-type ovarian tumour marker beta-2-microglobulin is regulated by the TGF-β signaling pathway.
abstract: BACKGROUND
  Beta-2-microglobulin (B2M), a light chain subunit of the major histocompatibility complex (MHC) class I complex, has been implicated in tumorigenesis. However, whether it is expressed in different epithelial-type ovarian tumours remains unknown. This study was performed to examine the expression of B2M in different histopathological types of ovarian tumours, to explore the function of B2M in ovarian cancer (OC) cells and to investigate the mechanisms underlying the regulation of B2M by the TGF-β signaling pathway.
  
  
  METHODS
  B2M expression in normal ovarian tissues and epithelia-type ovarian tumours was detected by immunohistochemistry and Western blot, followed by the analysis of association with clinical features. OC cells were transfected with B2M-siRNA and cell proliferation, migration and invasion were determined by WST-1 assay, wound healing assay and Transwell invasion assay, respectively. The regulation of B2M by the TGF-β signaling pathway in OC cells was examined by Western blot, ELISA and qRT-PCR.
  
  
  RESULTS
  We found that B2M was overexpressed in ovarian borderline and malignant tumours compared with benign tumours and normal controls, but was not associated with age, tumour size, lymph node metastasis and clinical stage. Knocking down of B2M led to a decrease in OC cell proliferation, migration and invasion. The expression of B2M was downregulated by TGF-β1 in OC cells, which was abolished in the presence of the inhibitor of TGF-β type I receptor.
  
  
  CONCLUSIONS
  Our findings suggest that B2M is a potential tissue biomarker and therapeutic target of borderline and malignant ovarian tumours and the dysregulation of B2M in these tumours may be mediated by the TGF-β signaling pathway.
authors.affiliation: Center Laboratory, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, People's Republic of China.|Department of Pathology, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pathology, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gui
authors.affiliation: Department of Obstetrics and Gynecology, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
authors.forename: Xulei
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Center Laboratory, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center Laboratory, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Daibing
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Pathology, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Ren
authors.affiliation: Center Laboratory, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai, 201508, People's Republic of China. guoxiong.xu@fudan.edu.cn.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. guoxiong.xu@fudan.edu.cn.
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D055815:Young Adult; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D001613:beta 2-Microglobulin
keywords: B2M; Biomarker; Epithelial ovarian cancer; TGF-β signaling; Therapeutic target; Tumorigenesis