title: CA IX is upregulated in CoCl2-induced hypoxia and associated with cell invasive potential and a poor prognosis of breast cancer.
abstract: Hypoxia, a common phenomenon during the development of malignant solid tumors including breast cancer, serves to propagate a cascade of molecular pathways triggered by hypoxia-inducible factor-1α (HIF-1α). Carbonic anhydrase IX (CA IX), one of the target genes of HIF-1α, has been reported to be involved in progression of malignant tumors. The objective of this study was to investigate the expression of HIF-1α and CA IX in hypoxia, involvement of CA IX in the regulation of migration and invasion/metastasis and its prognostic significance in breast cancer. We used cobalt chloride (CoCl2) as a hypoxia-mimetic agent and found that the expression of HIF-1α protein, CA IX mRNA and protein, is effectively upregulated, except for HIF-1α mRNA. Data showed that the elevated CA IX expression is closely related to in vitro cell migration and invasion, and the underlying mechanism of this process may be associated with epithelial-mesenchymal transition (EMT). The study of clinical tissue samples also demonstrated that CA IX is an independent prognostic marker that may serve as a useful clinical biomarker for predicting tumor progression and the invasion/metastasis of breast cancer. These results provide further insight into the role of CA IX in tumor progression and put forward further strong evidence as well as new consideration for CA IX target therapy.
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Chu
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Jin
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Zi-Jing
authors.initials: ZJ
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis* / Q000235:genetics; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation / Q000235:genetics; D003035:Cobalt / Q000633:toxicity; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D061986:MCF-7 Cells; D008875:Middle Aged; D011379:Prognosis; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003035:Cobalt; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C018021:cobaltous chloride