title: High Bak Expression Is Associated with a Favorable Prognosis in Breast Cancer and Sensitizes Breast Cancer Cells to Paclitaxel.
abstract: Breast cancer has become the leading cause of cancer-related death among women. A large number of patients become resistant to drug chemotherapy. Paclitaxel (Taxol) is an effective chemotherapeutic agent used to treat cancer patients. Taxol has been widely used in human malignancies including breast cancer because it can stabilize microtubules resulting in cell death by causing an arrest during the G2/M phase of the cell cycle. Pro-apoptotic Bcl-2 antagonist killer 1 (Bak) plays an important role in Taxol-induced apoptosis in breast cancer. In our present study, we investigated the expression of the Bak protein and clinicopathological correlations in a large sample of breast cancer tissues by immunohistochemistry. We found that the percentage of high scores of Bak expression in breast cancer was significantly lower than that of the non-cancerous breast control tissue. In addition, lower Bak expression was positively associated with the clinical TNM stage of breast cancer with a significant decrease in overall survival compared with those with higher Bak expression especially in the Luminal and HER2 subtypes. Importantly, higher Bak expression predicted a favorable clinical outcome in the cases treated with Taxol indicated by a higher overall survival than that of patients with lower Bak expression especially in Luminal and HER2 subtypes. Furthermore, these results were confirmed in vitro since overexpression of Bak sensitized breast cancer cells to Taxol by inhibiting proliferation and promoting apoptosis; in contrast, downregulation of Bak through siRNA transfection inhibited Taxol induced-apoptosis. Therefore, our results demonstrate that Bak acts as a sensitive biomarker and favorable prognostic factor for Taxol treatment in breast cancer. The restoration of Bak expression would be therapeutically beneficial for Taxol resistant breast cancer patients.
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Luo
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Xinye
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Heran
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
authors.forename: Qiuyuan
authors.initials: Q
authors.lastname: Wen
authors.affiliation: The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
authors.forename: Songqing
authors.initials: S
authors.lastname: Fan
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhao
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Shihe
authors.initials: S
authors.lastname: Jiang
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Third Xiang-Ya Hospital, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Peng
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, 36604, United States of America.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Phillips
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, 36604, United States of America.
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.affiliation: The Affiliated Tumor Hospital of Xiangya Medical School, Cancer Research Institute, Central South University, Changsha, Hunan, 410013, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation; D055815:Young Adult; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494772:BAK1 protein, human; D050998:bcl-2 Homologous Antagonist-Killer Protein; D017239:Paclitaxel