HIC-1 is a gene that is hypermethylated in
cancer, and commonly downregulated in human
breast cancer. However, the precise mechanisms and molecular pathways regulated by HIC-1 remain unclear. We assessed HIC-1 expression on a tissue microarray containing 80 cases of
breast cancer. We also analyzed its
biological function by restoring HIC-1 expression using 5-aza-2'
deoxycytidine (5-CdR) and small-activating RNAs for the reversal of HIC-1
tumor suppressive effects on MCF-7 and MDA-MB-231 cell lines. An Agilent Q44h global expressing microarray was probed after restoring the expression of HIC-1. Data demonstrated that HIC-1 expression was reduced significantly in
breast cancer tissues. HIC-1 immunohistochemistry resulted in mean staining scores in
cancer tissue and normal ductal epithelia of 3.54 and 8.2, respectively (p<0.01). 5-CdR partially reversed HIC-1 expression, and modulated cell growth and apoptosis. dsHIC1-2998, an saRNA, showed activating efficacy in
breast cancer cells. A group of differentially expressed genes were characterized by
cDNA microarray. Upon saRNA treatment, genes upregulated included those involved in immune activation, cell cycle interference, the induction of apoptosis, anti-
metastasis, and cell differentiation. Downregulated genes included oncogenes and those that play roles in cell invasion, cell growth, and cell division. Our findings may provide valuable resources not only for gene functional studies, but also for potential clinical applications to develop novel
drug targets.