BTG1 inhibits breast cancer cell growth through induction of cell cycle arrest and apoptosis

Zhu,Ran; Zou,Shi-Tao; Wan,Jian-Mei; Li,Wei; Li,Xin-Li; Zhu,Wei

doi:10.3892/or.2013.2697

BTG1 inhibits breast cancer cell growth through induction of cell cycle arrest and apoptosis

Authors:
- Ran Zhu
- Shi-Tao Zou
- Jian-Mei Wan
- Wei Li
- Xin-Li Li
- Wei Zhu
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Affiliations: School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China, Oncology Institute, Wuxi Fourth People's Hospital, Wuxi, Jiangsu 214062, P.R. China, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China , Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, P.R. China, School of Public Health, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China
Published online on: August 26, 2013 https://doi.org/10.3892/or.2013.2697
Pages: 2137-2144

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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.

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