title: Hepatoma-derived growth factor regulates breast cancer cell invasion by modulating epithelial--mesenchymal transition.
abstract: Hepatoma-derived growth factor (HDGF) participates in tumourigenesis but its role in breast cancer is unclear. We set out to elucidate the expression profile and function of HDGF during breast carcinogenesis. Immunoblot and immunohistochemical studies revealed elevated HDGF expression in human breast cancer cell lines and tissues. Nuclear HDGF labelling index was positively correlated with tumour grade, stage and proliferation index, but negatively correlated with survival rate in breast cancer patients. HDGF over-expression was associated with lymph node metastasis and represented an independent prognostic factor for tumour recurrence. Gene transfer studies were performed to elucidate the influence of cellular HDGF level on the malignant behaviour and epithelial-mesenchymal transition (EMT) of breast cancer cells. Adenovirus-mediated HDGF over-expression stimulated the invasiveness and colony formation of MCF-7 cells. Moreover, HDGF over-expression promoted breast cancer cell EMT by E-cadherin down-regulation and vimentin up-regulation. Conversely, HDGF knockdown by RNA interference in MDA-MB-231 cells attenuated the malignant behaviour and elicited EMT reversal by enhancing E-cadherin expression while depleting vimentin expression. Because HDGF is a secreted protein, we evaluated the cellular function of recombinant HDGF and found that exogenously supplied HDGF enhanced the invasiveness of breast cancer cells by down-regulating E-cadherin and up-regulating vimentin at transcriptional and translational levels. In contrast, blockade of HDGF secretion with an HDGF antibody inhibited the malignant behaviours and EMT. Finally, exogenous HDGF partially reversed benzyl isothiocyanate (BITC)-induced EMT suppression. HDGF over-expression may exert a prognostic role for tumour metastasis and recurrence in breast cancer by modulating EMT. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: San-Cher
authors.initials: SC
authors.lastname: Chen
authors.forename: Mei-Lang
authors.initials: ML
authors.lastname: Kung
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Jian-Ching
authors.initials: JC
authors.lastname: Wu
authors.forename: Hsiao-Mei
authors.initials: HM
authors.lastname: Kuo
authors.forename: Han-En
authors.initials: HE
authors.lastname: Tsai
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Lin
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.forename: Jong-Kang
authors.initials: JK
authors.lastname: Liu
authors.forename: Ming-Hsin
authors.initials: MH
authors.lastname: Yeh
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011994:Recombinant Proteins
chemical_list: D019138:Antibodies, Blocking; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D011994:Recombinant Proteins; C051610:hepatoma-derived growth factor