The new tumor suppressor genes ING: genomic structure and status in cancer.

The Inhibitor of Growth 1 (ING1) gene has been identified and characterized as a Type-II tumor suppressor gene (TSG). Subsequently, 4 additional members of the family were identified by homology search. ING proteins contain a nuclear localization sequence (NLS) and a plant homeo domain (PHD) finger motif in their C-terminus. These proteins are involved in numerous signaling pathways especially in 2 tumor suppressor pathways: apoptosis and senescence. In human tumors, several studies have shown that the expression of ING1 is frequently lost or downregulated. It occurs most frequently at the RNA level, and thus epigenetics mechanism could be involved. We summarize the current knowledge on ING proteins functions and their involvement in various signaling pathways. We also review the studies that have investigated the ING protein status in human tumors. The interest of ING proteins as biomarkers and their role in tumor initiation and progression is discussed.