Zhenglin Li1,2, Xiangdong Xu3, Meihua Luo4, Jiaojiao Hao1, Shilei Zhao5, Wendan Yu1, Xiangsheng Xiao6, Jiali Wu6, Fufu Zheng3, Miao Chen6, Yizhuo Li6, Ge Qin6, Yina Liao1, Xinrui Zhao1, Xinfa Yu4, Wei Guo1, Lijuan Zou1, Wuguo Deng1,6. 1. Institute of Cancer Stem Cell & The Second Affiliated Hospital, Dalian Medical University, Dalian, China. 2. The Central Hospital of Dalian, Dalian, China. 3. Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 4. Shunde Hospital of Southern Medical University, Foshan, China. 5. The First Affiliated Hospital of Dalian Medical University, Dalian, China. 6. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
Abstract
BACKGROUND/AIMS: Activator protein-2 (AP-2) transcription factors have been proved to be essential in maintaining cellular homeostasis and regulating the transformation from normal growth to neoplasia. However, the role of AP-2β, a key member of AP-2 family, in breast cancer is rarely reported. METHODS: The effect of AP-2 on cell growth, migration and invasion in breast cancer cells were measured by MTT, colony formation, wound-healing and transwell assays, respectively. The expression levels of AP-2β and other specific markers in breast cancer cell lines and tissue microarrays from the patients were detected using RT-PCR, Western blot and immunohistochemical staining. The regulation of AP-2β on tumor growth in vivo was analyzed in a mouse xenograft model. RESULTS: We demonstrated the tumor-promoting function of AP-2β in breast cancer. AP-2β was found to be highly expressed in breast cancer cell lines and tumor tissues of breast cancer patients. The shRNA-mediated silencing of AP-2β led to the dramatic inhibition of cell proliferation, colony formation ability, migration and invasiveness in breast cancer cells accompanied by the down-regulated expression of some key proteins involved in cancer progression, including p75, MMP-2, MMP-9, C-Jun, p-ERK and STAT3. Overexpression of AP-2β markedly up-regulated the levels of these proteins. Consistent with the in vitro study, the silencing or overexpression of AP-2β blocked or promoted tumor growth in the mice with xenografts of breast cancers. Notably, the high AP-2β expression levels was correlated with poor prognosis and advanced malignancy in patients with breast cancer. CONCLUSIONS: Our study demonstrates that AP-2β promotes tumor growth and predicts poor prognosis, and may represent a potential therapeutic target for breast cancer.
BACKGROUND/AIMS: Activator protein-2 (AP-2) transcription factors have been proved to be essential in maintaining cellular homeostasis and regulating the transformation from normal growth to neoplasia. However, the role of AP-2β, a key member of AP-2 family, in breast cancer is rarely reported. METHODS: The effect of AP-2 on cell growth, migration and invasion in breast cancer cells were measured by MTT, colony formation, wound-healing and transwell assays, respectively. The expression levels of AP-2β and other specific markers in breast cancer cell lines and tissue microarrays from the patients were detected using RT-PCR, Western blot and immunohistochemical staining. The regulation of AP-2β on tumor growth in vivo was analyzed in a mouse xenograft model. RESULTS: We demonstrated the tumor-promoting function of AP-2β in breast cancer. AP-2β was found to be highly expressed in breast cancer cell lines and tumor tissues of breast cancerpatients. The shRNA-mediated silencing of AP-2β led to the dramatic inhibition of cell proliferation, colony formation ability, migration and invasiveness in breast cancer cells accompanied by the down-regulated expression of some key proteins involved in cancer progression, including p75, MMP-2, MMP-9, C-Jun, p-ERK and STAT3. Overexpression of AP-2β markedly up-regulated the levels of these proteins. Consistent with the in vitro study, the silencing or overexpression of AP-2β blocked or promoted tumor growth in the mice with xenografts of breast cancers. Notably, the high AP-2β expression levels was correlated with poor prognosis and advanced malignancy in patients with breast cancer. CONCLUSIONS: Our study demonstrates that AP-2β promotes tumor growth and predicts poor prognosis, and may represent a potential therapeutic target for breast cancer.
Authors: Mohamed H Al-Sabri; Maryam Nikpour; Laura E Clemensson; Misty M Attwood; Michael J Williams; Mathias Rask-Anderson; Jessica Mwinyi; Helgi B Schiöth Journal: Cell Biosci Date: 2022-09-08 Impact factor: 9.584