ABSTRACT
<p><b>OBJECTIVE</b>To investigate the significance of Tiam1 in invasion and metastasis of breast carcinoma and its mechanisms.</p><p><b>METHODS</b>Immunohistochemistry was used to detect Tiam1 expression in tumor tissue of 126 breast carcinomas. Tiam1 was silenced by siRNA in breast carcinoma cell line MDA-MB-435, then the expressions of phosphor-ERK 1, ERK 2 and VEGF were detected, and electrophoretic mobility shift assay (EMSA) was used to examine the transcription activiy of AP-1.</p><p><b>RESULTS</b>There was a significant relationship between Tiam1 expression and lymph node metastasis (P < 0.05). Furthermore, after silencing of Tiam1, the expressions of phosphor-ERK 1, ERK 2 and VEGF were decreased, and the transcription activity of AP-1 was down-regulated in the MDA-MB-435 cells.</p><p><b>CONCLUSION</b>Tiam1 is closely related with invasion and metastasis of breast carcinoma, and the cascade Tiam1 through ERK, AP-1 and VEGF pathways may play an important role in enhancing angiogenesis, therefore, to promote invasion and metastasis of breast carcinoma.</p>
Subject(s)
Female , Humans , Breast Neoplasms , Metabolism , Pathology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Gene Silencing , Guanine Nucleotide Exchange Factors , Genetics , Metabolism , Lymphatic Metastasis , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Neoplasm Invasiveness , RNA, Messenger , Metabolism , RNA, Small Interfering , Genetics , Signal Transduction , T-Lymphoma Invasion and Metastasis-inducing Protein 1 , Transcription Factor AP-1 , Metabolism , Vascular Endothelial Growth Factor A , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of T lymphoma invasion and metastasis inducing factor 1 (Tiam1) in breast carcinomas, and explore its association with the clinicopathological features of breast carcinoma.</p><p><b>METHODS</b>Immunohistochemistry was used to detect Tiam1 expression in normal breast tissue and 126 breast carcinoma tissues, and the expression levels of Tiam1 mRNA and protein were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting, respectively.</p><p><b>RESULTS</b>The expression of Tiam1 was significantly higher in breast carcinomas than in normal breast tissue (P<0.05). Tiam1 expression was not correlated to the age of the patients or the histological type (P>0.05), but to lymph node metastasis and clinical stages of the tumor (P<0.01). Tiam1 mRNA and protein expressions were stronger in breast carcinoma cell line MDA-MB-435 with high metastatic potential than in breast carcinoma cell line MCF-7.</p><p><b>CONCLUSION</b>Tiam1 is closely related to the metastasis of breast carcinoma, and may play an important role in promoting metastasis of breast carcinoma.</p>