Gene cloning of the novel molecules associated with the differentiation of adenocarcinoma and the development of the molecular target therapy

点击翻译按钮获取中文摘要

A human adenocarcinoma cell line, TAKA-1, was established from ascites of a patient with peritoneal carcinomatosis of unknown primary site. TAKA-1 is highly tumorigenic in athymic nude mice and grows in suspension oas spherical single cells in vitro. Treatment of TAKA-1 cells with demethylating agent, 5-aza-2'-deoxycytidine, induced marked change in morphology from floating spherical to adherent epithelial. Treatment with 5-aza-2'-deoxycytidine also induced G1/S arrest leading to senescence. The cyclin-dependent kinase inhibitors (p161NK4a, p19INK4d and p21CIP1/WAF1), proapoptotic proteins (BAD, DAP-kinase and lipocalin 2) and proteins involved in integrin-mediated signaling (integrin alpha 3, 7b, 9, integrin bwta 4, 7, rho/rac GEF, rhoC, zyxin, MUC18) was up-regulated at mRNA level, while cyclines (cyclin D1, D3, A, C) and anti-apoptotic protein such as survivin was down-regulated at mRNA level after this treatment. To our knowledge, no cell lines have been reported which change in morphology so markedly as TAKA-1 after demethylation of DNA. TAKA-1 should provide a good experimental model to further study the molecular mechanism of peritoneal carcinomatosis and to efficiently screen new demethylating agents of DNA.