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Microarray profiling reveals calcium‐binding proteins S100A8 and S100A9 as candidate markers for invasive human breast epithelial cells
Author(s) -
Moon Aree,
Yong HaeYoung,
Song JaeIn,
Cukovic Daniela,
Salagrama Sridevi,
Kaplan David,
Putt David,
Kim Hyesook,
Dombkowski Alan,
Kim HyeongReh Choi
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1029.10
Subject(s) - gene knockdown , downregulation and upregulation , biology , s100a9 , cancer research , microarray analysis techniques , gene expression profiling , s100a8 , microarray , signal transduction , gene expression , microbiology and biotechnology , gene , genetics
The goal of the present study is to unveil the gene expression profile specific to the biological processes of human breast epithelial cell invasion and migration using an MCF10A model in which the H‐Ras or N‐Ras signaling pathway is constitutively activated. H‐Ras, but not N‐Ras, induces invasion/migration. H‐Ras‐mediated MCF10A invasion involves increased expression of MMP‐2 and ‐9. Analysis of whole human genome microarray revealed that 412 genes were differentially expressed among MCF10A, N‐Ras MCF10A and H‐Ras MCF10A cells. Two calcium‐binding proteins, S100A8 and S100A9, were prominently upregulated in an H‐Ras‐specific manner. Importantly, siRNA‐mediated knockdown of S100A8 or S100A9 expression significantly reduced H‐Ras‐mediated MCF10A cell invasion/migration. We further demonstrated that S100A8 was more closely associated with MMP‐9 expression mediated by ERKs pathway while S100A9 might play a major role in MMP‐2 upregulation which is dependent on p38MAPK pathway. Taken together, this study reveals S100A8 and S100A9 as candidate markers for metastatic potential of breast epithelial cells. Our gene profile data provide invaluable information which might be useful for identification of additional potential targets for prognosis and/or therapy of metastatic breast cancer [Supported by the NIEHS, NCI R41, USA and the Fostering Project of the Lab of Excellency, Korea].