Tumor suppressor genes (TSGs) and oncogenes represent the ying and the yang of cell growth, differentiation, and survival control. TSGs such as p53, the retinoblastoma (RB) gene product, and the cyclin kinase inhibitor (CKI) proteins p21 Cip-1/WAF1/mda6 (p21), p27 Kip-1 (p27), p16 INK4a (p16), and p19 ARF (p19), play the role of negative regulators of the cell cycle (1 –5 ). In contrast, mutation of protooncogenes such as the epidermal growth factor receptor (EGFR) (6 ), ErbB2 (Neu) (7 ), Ras (8 ,9 ), Raf-1 (10 ), PTEN (11 ,12 ), MKP-1 (13 ), and c-Myc (14 ) can promote cell cycle progression, in part by abrogating the negative regulation of the cell cycle by tumor suppressor genes.
