title: BTG1 inhibits breast cancer cell growth through induction of cell cycle arrest and apoptosis.
abstract: BTG1, which belongs to the BTG/Tob family, regulates cell cycle progression in a variety of cell types and appears to play roles in inhibiting proliferation, promoting apoptosis and stimulating cellular differentiation in multiple cell types. However, it remains unclear whether BTG1 is a breast cancer suppressor gene, and the role of BTG1 in breast cancer cell growth has not yet been determined. In the present study, we observed that BTG1 was weakly expressed in human breast tumors and in breast cancer cells (MCF-7 and MDA-MB-231). In addition, we investigated the potential effects of BTG1 on breast cancer cell proliferation, cell cycle distribution and apoptosis after stable transfection with the BTG1 expression vector. We found that overexpression of BTG1 inhibited cell proliferation, induced G0/G1 cell cycle arrest and promoted apoptosis. Further investigation indicated that overexpression of BTG1 was involved in the inhibition of the expression of cell cycle-related proteins, cyclin B1 and cyclin D1, and pro-apoptotic factors, Bax and caspase-3, and was also involved in the promotion of anti-apoptotic factor Bcl-2. In vivo, animal experiments showed that tumors overexpressing BTG1 displayed a slower growth rate than the control xenografts. TUNEL end staining assay revealed that BTG1 induced tumor necrosis and apoptosis. Taken together, our data revealed that, in breast cancer cells, BTG1 inhibits cell growth through induction of cell cycle arrest and apoptosis. These results indicate that BTG1 may be used as a novel therapeutic target for human breast cancer treatment.
authors: School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors: Ran
authors: R
authors: Zhu
authors: Shi-Tao
authors: ST
authors: Zou
authors: Jian-Mei
authors: JM
authors: Wan
authors: Wei
authors: W
authors: Li
authors: Xin-Li
authors: XL
authors: Li
authors: Wei
authors: W
authors: Zhu
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D006801:Humans; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C074086:BTG1 protein, human; D053148:Caspase 3