title: Liver kinase B1 enhances chemoresistance to gemcitabine in breast cancer MDA-MB-231 cells.
abstract: Liver kinase B1 (LKB1) is a well-known tumor suppressor gene in a variety of human cancers, including breast cancer. However, its role in gemcitabine resistance is unclear. Since gemcitabine in combination with other chemotherapeutic reagents is the first-line treatment in advanced breast cancer, the aim of the present study was to determine the effect of ectopic expression of LKB1 on chemosensitivity to gemcitabine in the breast cancer MDA-MB-231 cell line. Increasing the expression of LKB1 was found to directly correlate with gemcitabine chemoresistance. Although LKB1 suppressed the cell proliferation rate and clonogenicity in the absence of gemcitabine, it increased the median inhibitory concentration of gemcitabine and clonogenicity of cells in the presence of gemcitabine. Mechanistic analysis indicated that LKB1 was able to protect cells from DNA damage caused by gemcitabine. Furthermore, it was found that LKB1 induced a significant upregulation of cytidine deaminase expression, an important enzyme that accelerates gemcitabine catabolization. Overall, dual characteristics of LKB1 were identified: Suppressing cell growth in normal conditions and enhancing chemoresisitance to gemcitabine, possibly by accelerating degradation of gemcitabine, and protecting cells from DNA damage caused by gemcitabine.
authors.affiliation: Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University, School of Medicine, Shanghai 200040, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xia
authors.affiliation: Department of General Surgery, Affiliated Union Hospital of Fujian Medical University, Union Clinical School, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Fugui
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University, School of Medicine, Shanghai 200040, P.R. China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University, School of Medicine, Shanghai 200040, P.R. China.
authors.forename: Beiqi
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University, School of Medicine, Shanghai 200040, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University, School of Medicine, Shanghai 200040, P.R. China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University, School of Medicine, Shanghai 200040, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhuang
keywords: DNA damage; breast neoplasms; cytidine deaminase; gemcitabine; liver kinase B1