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Moon, Aree; Yong, Hae‐Young; Song, Jae‐In; Cukovic, Daniela; Salagrama, Sridevi; Kaplan, David; Putt, David; Kim, Hyesook; Dombkowski, Alan; Kim, Hyeong‐Reh Choi
The FASEB journal, 03/2008, Letnik: 22, Številka: S1Journal Article
Abstract only 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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