Trefoil Factor-1 (TFF1) Enhances Oncogenicity of Mammary Carcinoma Cells

• Published in: Endocrinology (Philadelphia) 2009-10, Vol.150 (10), p.4473-4483
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Anchorages; Animals; Autocrine signalling; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma - metabolism; Carcinoma - pathology; Cell culture; Cell Cycle; Cell Line, Tumor; Cell migration; Cell morphology; Cell Movement; Cell number; Cell Proliferation; Cell size; Cell Survival; Cell viability; Disease Progression; Female; Functionals; Gene expression; Humans; Mammary gland; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neutralization; Polyclonal antibodies; RNA Interference; RNA, Messenger - metabolism; RNA-mediated interference; Trefoil factor; Trefoil Factor-1; Tumor Suppressor Proteins - immunology; Tumor Suppressor Proteins - metabolism; Xenografts; Xenotransplantation
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2009-0066

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. Secretion of trefoil factor-1 by mammary carcinoma cells promotes tumor progression; therapeutic targeting of TFF1 should provide a novel approach for treatment of mammary carcinoma.