B‑cell translocation 1 gene inhibits cellular metastasis‑associated behavior in breast cancer.
B-cell translocation gene 1 (BTG1) is a member of the BTG/transducer of ERBB2 family, which regulates cell cycle progression in a variety of cell types and may have a role in inhibiting proliferation, promoting apoptosis and stimulating cellular differentiation in numerous cell types. However, the role of BTG1 in cancer metastasis is yet to be elucidated. In the present study, analysis of clinical specimens revealed that BTG1 mRNA levels were lower in lymph node metastases than those in benign breast tumors and normal human breast tissue. The effect of BTG1 on the metastatic behavior of breast cancer cells following stable transfection with a BTG1 expression vector was also investigated. The overexpression of BTG1 was observed to inhibit cell adhesion, migration and invasion. Furthermore, the overexpression of BTG1 was found to be involved in the inhibition of the metastasis-related proteins matrix metalloproteinase-2 and -9, as well as the promotion of the cell-cell adhesion-associated protein E-cadherin. In syngeneic nude mice breast tumor models, hepatic metastasis and angiogenesis were observed in the mice injected with the control cells, but not in those injected with pcDNA3-BTG1 cells. Immunohistochemistry revealed that overexpression of BTG1 decreased vascular endothelial growth factor expression in tumors. To the best of our knowledge, this is the first study to show that BTG1 overexpression decreases migration and invasion of breast cancer cells and thereby inhibits distant metastasis in mice breast tumor models.
Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Wei
W
Li
Oncology Institute, Wuxi Fourth People's Hospital, Wuxi, Jiangsu 214062, P.R. China.
Shi-Tao
ST
Zou
School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
Ran
R
Zhu
School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
Jian-Mei
JM
Wan
Advanced Health Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
Yan
Y
Xu
Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Hao-Rong
HR
Wu
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics
D009363:Neoplasm Proteins; C074086:BTG1 protein, human