Abstract
Abstract Gene amplification is a major mechanism used by cancer cells to increase gene expression and subsequently gain a growth and survival advantage. Previously, we identified a novel amplicon at 9p23-24 region in human esophageal and breast cancer and originally cloned a novel gene GASC1 (Gene Amplified in Squamous Cell Carcinoma 1) from this amplicon. Accumulating evidence suggests common amplicons that occur in breast and other cancers contain multiple oncogenes that could play a role in cancer initiation and progression. In the current study, we aimed to comprehensively characterize the 9p23-24 amplified genes in human breast cancer. We performed array CGH analysis on a panel of cancer cell lines with the Agilent 244K microarray chip and narrowed the shortest region of overlapping (SRO) of the 9p23-24 amplicon to ∼2 Mb. Eleven genes within the SRO regions were examined for their mRNA expression by quantitative RT-PCR (qRT-PCR). Based on statistical association between copy number and expression, we confirmed GASC1 as a top candidate oncogene and identified three new potential oncogenes, UHRF2, KIAA1432 and C9orf123. Our more recent studies indicated that GASC1 is a member of a new class of oncogenes that are involved in the deregulation of histone methylation in cancer cells. We found that GASC1 induces the expression of core stemness transcription factors NANOG, SOX2 and OCT4, as well as classical oncogenes, including NOTCH1 and MYC, in breast cancer cells. On the other hand, UHRF2 encodes a nuclear protein that is involved in cell-cycle regulation. Knocking down UHRF2 slowed cell growth and inhibited colony formation of 9p23-24 amplified breast cancer cells. Furthermore, we demonstrated that expression levels of key tumor suppressing genes, including p16/INK4a, p21/WAF1 and p27/KIP1, were increased after knocking down UHRF2 in breast cancer cells. Collectively, our studies support the notion that the 9p23-24 amplicon contains multiple candidate oncogenes and may play an important role in human tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4700. doi:10.1158/1538-7445.AM2011-4700
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