Cyclin-dependent kinase 저해 단백질 p16INK4A의 인체 암세포에서의 세포사멸 유도 활성

Abstract

A Cyclin-Dependent Kinase Inhibitor, p16INK4A, Induces Apoptosis in The Human Cancer Cells. Kim, Min-Kyoung and Chul-Hoon Lee*. Department of Medical Genetics, Hanyang University College of Medicine, Seoul 133-791, Korea - Previously, we synthesized a novel Cyclin-dependent kinase inhibitor, MCS-5A. Also, we investigated the involvement of cell cycle regulatory events during MCS-5A-mediated apoptosis in HL-60(+p16/-p53) cells with up-regulation of p16 protein expression. In contrast, apoptosis was not observed in A549(-p16/+p53) cells. Therefore we propose that p16INK4A is a key enzyme for inducing apoptosis. In the present studies, we have explored the mechanism of p16INK4A-mediated cytotoxicity and the role of p16INK4A overexpression in the induction of apoptosis in human tumor cells. The tumor suppressor gene p16INK4A is known as a cyclin-dependent kinase inhibitor (CKI) and cell cycle regulator. We expressed wild type p16INK4A in pcDNA3.1 vector and then transfected into non-small cell lung cancer (NSCLC) cell expressing different statue of p16INK4A, p53 gene[A549(-p16/+p53), H1299(-p16/-p53) and HeLa (+p16/+p53)cell line]. TUNEL assay (including propidium iodide staining following transfection of these cell line with pcDNA3.1-p16) indicate that p16INK4A-mediated cytotoxicity was associated with apoptosis. This is supported by studies demonstrating an induction of caspase 3 cleavage due to the transfection of A549, H1299 and HeLa cells with pcDNA3.1-p16. These results suggest that p16INK4A has a new function of inducing apoptosis which is not related with the function of tumor suppressor gene p.53