Kontani Keiichi, Chano Tokuhiro, Ozaki Yoshitomo, Tezuka Noriaki, Sawai Satoru, Fujino Shozo, Saeki Yukikazu, Okabe Hidetoshi
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Int J Mol Med. 2003 Nov;12(5):767-9.
RB1-inducible Coiled-Coil 1 (RB1CC1) is a putative transcription factor that functions as a key regulator of retinoblastoma 1 (RB1). RB1CC1 mutations lacking this function are involved in the tumorigenesis of breast cancers. RB1CC1 is distributed in various tissues other than the breast, and is thought to play a biological role in controlling cell growth and progression of various cancers. The present study examined the correlation between RB1CC1 and cell cycle-related molecules in human neoplastic cells, and the ratios of cells at various phases of the cell cycle were verified in the RB1CC1-transduced human leukemic cell lines, K562 and Jurkat. The results showed that RB1CC1 was synchronously expressed with RB1 in various cell lines and that introducing RB1CC1 induced RB1 expression in human leukemic cell lines, although independently of the other molecules. Western blotting showed that underphosphorylated forms of RB1 were elicited by RB1CC1, whereas E2F1 was not affected. Cell cycle analysis demonstrated that G2-M phases were suppressed in RB1CC1-transduced cells. These data suggested that RB1CC1 induces the expression of RB1, especially of underphosphorylated forms, then suppresses cell cycle progression in human neoplastic cells.
RB1诱导卷曲螺旋蛋白1(RB1CC1)是一种假定的转录因子,作为视网膜母细胞瘤1(RB1)的关键调节因子发挥作用。缺乏这种功能的RB1CC1突变与乳腺癌的肿瘤发生有关。RB1CC1分布于乳腺以外的各种组织中,被认为在控制各种癌症的细胞生长和进展中发挥生物学作用。本研究检测了RB1CC1与人类肿瘤细胞中细胞周期相关分子之间的相关性,并在RB1CC1转导的人类白血病细胞系K562和Jurkat中验证了细胞周期各阶段细胞的比例。结果表明,RB1CC1在各种细胞系中与RB1同步表达,并且在人类白血病细胞系中引入RB1CC1可诱导RB1表达,尽管与其他分子无关。蛋白质印迹法显示,RB1CC1引发了RB1的低磷酸化形式,而E2F1未受影响。细胞周期分析表明,RB1CC1转导的细胞中G2-M期受到抑制。这些数据表明,RB1CC1诱导RB1的表达,尤其是低磷酸化形式的RB1,然后抑制人类肿瘤细胞的细胞周期进程。