title: NES1/KLK10 gene represses proliferation, enhances apoptosis and down-regulates glucose metabolism of PC3 prostate cancer cells.
abstract: The normal epithelial cell-specific-1 (NES1) gene, also named as KLK10, is recognised as a novel putative tumour suppressor in breast cancer, but few studies have focused on the function of KLK10 in human prostate cancer. Our study confirms that the expression of KLK10 in prostate cancer tissue and cell lines (PC3, DU145, and LNCaP clone FGC) is low. Given that the androgen-independent growth characteristic of the PC3 cell line is more similar to clinical castration-resistant prostate cancer, we studied the role of KLK10 in PC3. In vitro and in vivo assays showed that over-expressing KLK10 in PC3 could decelerate tumour proliferation, which was accompanied with an increase in apoptosis and suppression of glucose metabolism. The related proteins, such as Bcl-2 and HK-2, were down-regulated subsequently. Furthermore, by up-regulating Bcl-2 or HK-2 respectively in the PC3-KLK10 cell line, we observed a subsequent increase of cell proliferation and a synchronous up-regulation of HK-2 and Bcl-2. Besides, KLK10 expression was also increased by Bcl-2 and HK-2, which suggests that there is a negative feedback loop between KLK10 and Bcl-2/HK-2. Thus, our results demonstrated that KLK10 may function as a tumour suppressor by repressing proliferation, enhancing apoptosis and decreasing glucose metabolism in PC3 cells.
authors.affiliation: Department of Nuclear Medicine, Rui jin Hospital, School of Medicine, Shanghai JiaoTong University; 197 Ruijin Second Road, Shanghai 200025, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, School of Medicine, Shanghai JiaoTong University; 280 Chongqing South Road, Shanghai 200025, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Pathology, Rui jin Hospital, School of Medicine, Shanghai JiaoTong University; 197 Ruijin Second Road, Shanghai 200025, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Nuclear Medicine, Xin hua Hospital, School of Medicine, Shanghai JiaoTong University; 1665 Kongjiang Road, Shanghai 200025, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, School of Medicine, Shanghai JiaoTong University; 280 Chongqing South Road, Shanghai 200025, China.
authors.forename: Hanzhang
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, School of Medicine, Shanghai JiaoTong University; 280 Chongqing South Road, Shanghai 200025, China.
authors.forename: Dongjun
authors.initials: D
authors.lastname: Qin
authors.affiliation: Department of Nuclear Medicine, Rui jin Hospital, School of Medicine, Shanghai JiaoTong University; 197 Ruijin Second Road, Shanghai 200025, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, School of Medicine, Shanghai JiaoTong University; 280 Chongqing South Road, Shanghai 200025, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Nuclear Medicine, Rui jin Hospital, School of Medicine, Shanghai JiaoTong University; 197 Ruijin Second Road, Shanghai 200025, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Li
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D019788:Fluorodeoxyglucose F18; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D019788:Fluorodeoxyglucose F18; D006593:Hexokinase; C100936:KLK10 protein, human; D007610:Kallikreins; D053148:Caspase 3; D005947:Glucose