Biochemical & Biophysical Research Communications, 2007, 361(1):169-175.

Genistein induces the metastasis suppressor kangai-1 which mediates its anti-invasive effects in TRAMP cancer cells

Lara H. El Touny , Partha P. Banerjee

Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, District of Columbia

Previous studies demonstrated a direct correlation with loss of kangai-1 (KAI1), a metastasis suppressor, and poor prognosis in human prostate and other cancers. In this study, we have characterized the age-dependent downregulation of KAI1 in the TRAMP model which was reversed when mice were fed a genistein-enriched diet. We demonstrated here that doses of genistein (5 and 10 microM)--achievable by supplement intake--significantly induced the expression of KAI1, both at the mRNA and protein levels (up to 2.5-fold), and decreased the invasiveness of TRAMP-C2 cells >2.0-fold. We have pinpointed KAI1 as the invasion suppressor, since its knockdown by siRNA restored the invasive potential of genistein-treated TRAMP-C2 cells to control levels. This work provides the first evidence that genistein treatment may counteract KAI1 downregulation, which is observed in many cancer types and therefore, could be used in anti-metastatic therapies.

美国《生化和生物物理研究通讯》，2007年

金雀异黄素诱导转导抑制因子kangai-1，介导其在TRAMP癌细胞中的抗侵袭作用

劳拉 H EI 托尼，派瑟 P 班妮杰

哥伦比亚特区华盛顿乔治敦大学医学中心生物化学和分子与细胞生物学系

以前的研究表明与人前列腺癌和其他癌症中的转移抑制因子kangai-1（KAI1）的丧失与预后不佳直接相关。 在这项研究中，我们已经表征了TRAAM模型中KAI1的年龄依赖性下调，当小鼠饲喂富含染料木素的饮食时，其反转。 我们在这里展示了通过补充摄入可以实现的剂量的染料木素（5和10 microM） - 在mRNA和蛋白质水平（高达2.5倍）上显着诱导KAI1的表达，并降低TRAMP- C2细胞> 2.0倍。 我们已经将KAI1定位为侵袭抑制因子，因为siRNA的敲低可以恢复染料木黄酮治疗的TRAMP-C2细胞的侵袭潜能来控制水平。 这项工作提供了第一个证据表明，染料木素治疗可能抵消KAI1下调，这在许多癌症类型中被观察到，因此可以用于抗转移治疗。