title: Serine protease PRSS23 is upregulated by estrogen receptor α and associated with proliferation of breast cancer cells.
abstract: Serine protease PRSS23 is a newly discovered protein that has been associated with tumor progression in various types of cancers. Interestingly, PRSS23 is coexpressed with estrogen receptor α (ERα), which is a prominent biomarker and therapeutic target for human breast cancer. Estrogen signaling through ERα is also known to affect cell proliferation, apoptosis, and survival, which promotes tumorigenesis by regulating the production of numerous downstream effector proteins.In the present study, we aimed to clarify the correlation between and functional implication of ERα and PRSS23 in breast cancer. Analysis of published breast cancer microarray datasets revealed that the gene expression correlation between ERα and PRSS23 is highly significant among all ERα-associated proteases in breast cancer. We then assessed PRSS23 expression in 56 primary breast cancer biopsies and 8 cancer cell lines. The results further confirmed the coexpression of PRSS23 and ERα and provided clinicopathological significance. In vitro assays in MCF-7 breast cancer cells demonstrated that PRSS23 expression is induced by 17β-estradiol-activated ERα through an interaction with an upstream promoter region of PRSS23 gene. In addition, PRSS23 knockdown may suppress estrogen-driven cell proliferation of MCF-7 cells.Our findings imply that PRSS23 might be a critical component of estrogen-mediated cell proliferation of ERα-positive breast cancer cells. In conclusion, the present study highlights the potential for PRSS23 to be a novel therapeutic target in breast cancer research.
authors.affiliation: Department of Medical Science, Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Hau-Shien
authors.initials: HS
authors.lastname: Chan
authors.forename: Shing-Jyh
authors.initials: SJ
authors.lastname: Chang
authors.forename: Tao-Yeuan
authors.initials: TY
authors.lastname: Wang
authors.forename: Hung-Ju
authors.initials: HJ
authors.lastname: Ko
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Lin
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Lin
authors.forename: Kuo-Ming
authors.initials: KM
authors.lastname: Chang
authors.forename: Yung-Jen
authors.initials: YJ
authors.lastname: Chuang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016000:Cluster Analysis; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056726:Genetic Association Studies; D006801:Humans; D046228:Microarray Analysis; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D057057:Serine Proteases / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004958:Estradiol; D057057:Serine Proteases; C572443:PRSS23 protein, human; D012697:Serine Endopeptidases