Overexpression of the Replication Licensing Regulators hCdt1 and hCdc6 Characterizes a Subset of Non-Small-Cell Lung Carcinomas

摘要: Replication licensing ensures once per cell cycle replication and is essential for genome stability. Overexpression of two key factors, Cdc6 Cdt1, leads to overreplication chromosomal instability (CIN) in lower eukaryotes recently human lines. In this report, we analyzed hCdt1, hCdc6, hGeminin, the hCdt1 inhibitor expression, a series non-small-cell lung carcinomas, investigated putative relations with G1/S phase regulators, tumor kinetics, ploidy. This first study these fundamental elements primary carcinomas. We herein demonstrate elevated levels (more than fourfold) hCdc6 43% 50% neoplasms, respectively, whereas aberrant expression hGeminin was observed 49% cases (underexpression, 12%; overexpression, 37%). positively correlated E2F-1 (P = 0.001 P 0.048, respectively). Supportive link between provide evidence that up-regulates promoter cultured mammalian cells. Interestingly, overexpression statistically related increased 0.025). Regarding kinetic ploidy status hCdt1- and/or hCdc6-overexpressing tumors, p53-mutant exhibited significantlyincreased growth values (Growth Index; GI) aneuploidy/CIN compared those bearing intact p53 0.008 GI, CIN). The significance results underscored by fact latter parameters were independent within hCdt1-hCdc6 normally expressing cases. Cumulatively, above suggest synergistic effect mutant-p53 over CIN