SALL4 is Essential for Cancer Cell Proliferation and is Overexpressed at Early Clinical Stages in Breast Cancer

Few target molecules have been identified that enable the diagnosis of breast cancer with a high sensitivity and specificity, especially in the early clinical stages of cancer. Here, we present the first evidence for diagnostic performance of gene expression for SALL4, a transcription factor that plays an essential role in the embryonic development and self-renewal of embryonic stem (ES) cells, in breast cancer. The sensitivity and specificity of SALL4 was 80.4 and 80.0%, respectively, as estimated using the cut-off value obtained from the analysis of the receiver operating characteristic curve. Furthermore, comparison of paired cancer and non-cancer tissues from the same breast cancer patient revealed elevated SALL4 mRNA levels in 86.1% (31/36) of the specimens. No obvious correlations were detected between clinicopathological factors and SALL4 mRNA expression; however, SALL4 mRNA was expressed at a high level even in the early clinical stages of the cancer. An siRNA experiment to determine the significance of SALL4 expression showed complete inhibition of proliferation in breast cancer MCF7 cells. This inhibitory effect of siRNA was induced by cell cycle arrest mainly at the G1 phase, leading to increased cell volume. These results suggest that SALL4 mRNA may be a new tool to support the diagnosis of breast cancer, and it may also represent a novel therapeutic target.