title: Correlation of Wilms' tumor 1 isoforms with HER2 and ER-α and its oncogenic role in breast cancer.
abstract: BACKGROUND
  Wilms' tumor 1 (WT1) gene has different functional properties depending on the isoform type. This gene correlates with cell proliferation in various types of cancer. Here, we investigated the expression of WT1 isoforms in breast cancer tissues, and focused on the oncogenic role through estrogen receptor-alpha (ER-α) and human epidermal growth factor receptor 2 (HER2).
  
  
  METHODS
  Expression of WT1(17AA+) and (17AA-) was investigated in adjacent normal breast and breast cancer using Reverse transcription-polymerase chain reaction and western blotting. The correlation of WT1 isoforms with HER2 and ER-α was examined using MCF-7 cells stably-overexpressing WT1s and siRNA against WT1 gene.
  
  
  RESULTS
  The expression of WT(17AA-) was significantly found in adjacent normal breast tissues. A mixture of WT1(17AA+) and WT1(17AA-) were highly expressed in breast carcinoma tissues. MCF-7 cells overexpressing WT1+/+ and WT1+/- represented strong expression of ER-α and HER2. Moreover, the silencing of WT1+/+ and WT1+/- resulted in a decrease of both ER-α and HER2 and led to a decrease of cell numbers.
  
  
  CONCLUSIONS
  Our results suggest that WT1(17AA+) was exhibited dominantly in breast carcinoma tissues. WT1+/+ and WT1+/- correlated with the high expression of ER-α and HER2, leading to cell proliferation and might be involved in cancer development and progression.
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat-Yai, Songkhla, 90110, Thailand. gpotchan@medicine.psu.ac.th.
authors.forename: Tapanawan
authors.initials: T
authors.lastname: Nasomyon
authors.forename: Srila
authors.initials: S
authors.lastname: Samphao
authors.forename: Surasak
authors.initials: S
authors.lastname: Sangkhathat
authors.forename: Somrit
authors.initials: S
authors.lastname: Mahattanobon
authors.forename: Potchanapond
authors.initials: P
authors.lastname: Graidist
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D025721:WT1 Proteins; C506487:ESR1 protein, human; C508053:ERBB2 protein, human
keywords: ER-α; HER2; WT1; breast cancer