デグチ　アツコ   Deguchi Atsuko   出口　敦子    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Induction of G1 arrest and selective growth inhibition by lactacystin in human umbilical vein endothelial cells.
掲載誌名	正式名：Anticancer Research ISSNコード：17917530
掲載区分	国外
巻・号・頁	19(5B),pp.3961-3968
著者・共著者	Kumeda S, Deguchi A, Toi M, Omura S, and Umezawa K.
担当区分	2nd著者
発行年月	1999
概要	In search for angiogenesis inhibitors, we tested protease and proteasome inhibitors for the induction of G1 arrest and selective inhibition of growth of human umbilical vein endothelial cells (HUVECs). Serine protease-, cysteine protease-, aspartate protease-, and aminopeptidase-inhibitors did not inhibit bFGF/FBS-induced S-phase induction in HUVECs, but a proteasome inhibitor, lactacystin did inhibit it reversibly. Lactacystin increased the cellular level of p53 and cdk2-associated p21WAF1/CIP1 leading to cdk2 inactivation. In addition to the angiogenesis inhibitor TNP-470, lactacystin also inhibited the growth of HUVECs selectively at about a 20 times lower concentration than that of other human cell lines, including normal fibroblasts and carcinoma cells. Lactacystin induced p53-dependent p21WAF1/CIP1 expression at lower concentrations in HUVECs than in other cells. These cellular effects were also observed with a tripeptide-type proteasome inhibitor, N-Ac-Leu-Leu-norleucinal.