Amiry Naeem, Kong Xiangjun, Muniraj Nethaji, Kannan Nagarajan, Grandison Prudence M, Lin Juan, Yang Yulu, Vouyovitch Cécile M, Borges Sahra, Perry Jo K, Mertani Hichem C, Zhu Tao, Liu Dongxu, Lobie Peter E
The Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Endocrinology. 2009 Oct;150(10):4473-83. doi: 10.1210/en.2009-0066. Epub 2009 Jul 9.
The functional role of autocrine trefoil factor-1 (TFF1) in mammary carcinoma has not been previously elucidated. Herein, we demonstrate that forced expression of TFF1 in mammary carcinoma cells resulted in increased total cell number as a consequence of increased cell proliferation and survival. Forced expression of TFF1 enhanced anchorage-independent growth and promoted scattered cell morphology with increased cell migration and invasion. Moreover, forced expression of TFF1 increased tumor size in xenograft models. Conversely, RNA interference-mediated depletion of TFF1 in mammary carcinoma cells significantly reduced anchorage-independent growth and migration. Furthermore, neutralization of secreted TFF1 protein by polyclonal antibody decreased mammary carcinoma cell viability in vitro and resulted in regression of mammary carcinoma xenografts. We have therefore demonstrated that TFF1 possesses oncogenic functions in mammary carcinoma cells. Functional antagonism of TFF1 can therefore be considered as a novel therapeutic strategy for mammary carcinoma.
自分泌三叶因子-1（TFF1）在乳腺癌中的功能作用此前尚未阐明。在此，我们证明，乳腺癌细胞中TFF1的强制表达导致细胞增殖和存活增加，从而使细胞总数增加。TFF1的强制表达增强了不依赖贴壁的生长，并促进了分散的细胞形态，同时细胞迁移和侵袭增加。此外，TFF1的强制表达增加了异种移植模型中的肿瘤大小。相反，RNA干扰介导的乳腺癌细胞中TFF1的缺失显著降低了不依赖贴壁的生长和迁移。此外，多克隆抗体对分泌的TFF1蛋白的中和作用降低了体外乳腺癌细胞的活力，并导致乳腺癌异种移植瘤消退。因此，我们证明TFF1在乳腺癌细胞中具有致癌功能。因此，TFF1的功能拮抗作用可被视为一种新的乳腺癌治疗策略。
