Loss of annexin A1 expression in human breast cancer detected by multiple high-throughput analyses |
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Authors: | Dejun Shen Zugen Chen Victor Lonsberry David Chia Lee Goodglick Jeffrey A Gornbein |
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Institution: | a Gonda/UCLA Breast Cancer Research Laboratory, Department of Surgery, Revlon/UCLA Breast Center, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA b Department of Human Genetics, UCLA, David Geffen School of Medicine, Los Angeles, CA 90095, USA c UCLA Department of Pathology and Laboratory Medicine and Jonsson Comprehensive Cancer Center, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA d Department of Biomathematics, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA |
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Abstract: | To test the efficacy of combined high-throughput analyses (HTA) in target gene identification, screening criteria were set using >fivefold difference by microarray and statistically significant changes (p < 0.01) in SAGE and EST. Microarray analysis of two normal and seven breast cancer samples found 129 genes with >fivefold changes. Further SAGE and EST analyses of these genes identified four qualified genes, ERBB2, GATA3, AGR2, and ANXA1. Their expression pattern was validated by RT-PCR in both breast cell lines and tissue samples. Loss of ANXA1 in breast cancer was further confirmed at mRNA level by Human Breast Cancer Tissue Profiling Array and at protein level by immunohistochemical staining. This study demonstrated that combined HTA effectively narrowed the number of genes for further study, while retaining the sensitivity in identifying biologically important genes such as ERBB2 and ANXA1. A distinctive loss of ANXA1 in breast cancer suggests its involvement in maintaining normal breast biology. |
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Keywords: | Annexin A1 Breast cancer-related genes Microarray Multiple high-throughput analysis SAGE EST CGAP |
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