Early Growth Response-1 Suppresses Human Fibrosarcoma Cell Invasion and Angiogenesis

Cancer Genomics - Proteomics

SHIYONG LI¹  RUOCHUN HUANG²  WEIMIN YANG²  RUO-PAN HUANG²  LIPAI CHEN²  CHEN YAO³ 

[1] epartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.epartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.epartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.;epartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.epartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.epartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.;epartment of Thyroid and Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Chinaepartment of Thyroid and Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Chinaepartment of Thyroid and Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

关键词: Egr-1;    fibrosarcoma;    angiogenesis;    invasion;    metastasis;    protein arrays;    TIMP-2;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

The development of malignant tumors is the result of sequential genetic and epigenetic lesions that lead to alterations in a number of gene expressions, which are primarily controlled by transcription factors. A growing body of evidence suggests that early growth response-1 (Egr-1), a transcription factor, may function as a tumor suppressor. Here, the possible role of Egr-1 in the suppression of tumor cell invasion, angiogenesis and metastasis was investigated. Expression of Egr-1 significantly reduced the invasion of human fibrosarcoma cells through matrigel. Mouse embryonic fibroblasts, from Egr-1 knockout mice, also showed increased invasion through matrigel compared with MEFs from wild-type mice. Conditioned medium from Egr-1-transfected cells compared with control transfected cells also reduced proliferation, invasion through matrigel and tube formation of human umbilical cord vein endothelial cells and human microvascular endothelial cells. In addition, Egr-1-transfected cells inhibited vessel formation in mouse skin plug assays. To study the possible molecular mechanisms responsible for this function, the expression of multiple cytokines, chemokines, growth factors and angiogenic factors were examined by using human cytokine antibody array technology it was observed that tissue inhibitor of metalloproteinase-2 (TIMP-2) expression was up-regulated in Egr-1-transfected cells. Addition of Egr-1-transfected cell conditioned medium and TIMP-2 recombinant protein suppressed fibrosarcoma cell invasion. In summary, it was shown that Egr-1 may have novel functions in the suppression of tumor cell invasion and angiogenesis, while TIMP-2 may be involved in the suppression of tumor cell invasion and angiogenesis in Egr-1-transfected cells.

【 授权许可】

Unknown