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    Cancer Res. 2010 Nov 1;70(21):8487-97. Epub 2010 Oct 12.

    Transforming properties of 8p11-12 amplified genes in human breast cancer.

    Yang ZQ, Liu G, Bollig-Fischer A, Giroux CN, Ethier SP.

    Source

    Breast Cancer Program and Systems and Computational Biology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA. yangz@karmanos.org

    Abstract

    Amplification of the 8p11-12 region has been found in about 15% of human breast cancers and is associated with poor prognosis. Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12 amplicon to identify candidate oncogenes in breast cancer. We identified 21 candidate genes and provided evidence that three genes, namely, LSM-1, TC-1, and BAG4, have transforming properties when overexpressed. In the present study, we systematically investigated the transforming properties of 13 newly identified 8p11-12 candidate oncogenes in vitro. WHSC1L1, DDHD2, and ERLIN2 were most potently transforming oncogenes based on the number of altered phenotypes expressed by the cells. WHSC1L1 contains a PWWP-domain that is a methyl-lysine recognition motif involved in histone code modification and epigenetic regulation of gene expression. Knockdown of WHSC1L1 in 8p11-12-amplified breast cancer cells resulted in profound loss of growth and survival of these cells. Further, we identified several WHSC1L1 target genes, one of which is iroquois homeobox 3 gene (IRX3), a member of the Iroquois homeobox transcription factor family.

    ©2010 AACR.

    PMID:
    20940404
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC3089754
    Free PMC Article

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