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NES1/KLK10 gene represses proliferation, enhances apoptosis and down-regulates glucose metabolism of PC3 prostate cancer cells.

Hu J, Lei H, Fei X, Liang S, Xu H, Qin D, Wang Y, Wu Y, Li B - Sci Rep (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Rui jin Hospital, School of Medicine, Shanghai JiaoTong University; 197 Ruijin Second Road, Shanghai 200025, China.

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.

No MeSH data available.


Related in: MedlinePlus

Up-regulation of KLK10 negatively regulates Bcl-2 and HK-2 expression.(A) CCK-8 cell proliferation assay showed that cell proliferation significantly increased in the Bcl-2- or HK-2-over-expressing PC3-KLK10 cell line compared with the PC3-KLK10 empty vector transfecting cell line (P < 0.001). (B) In the Bcl-2-over-expressing PC3-KLK10 cell line, the expression levels of both HK-2 and KLK10 increased. (C) In the HK-2-over-expressing PC3-KLK10 cell line, the expression levels of Bcl-2 and KLK10 also significantly increased. (D) Potential relationship diagram of KLK10, Bcl-2 and HK-2: the up-regulation of KLK10 might negatively regulate Bcl-2 and HK-2 expression; the expression of HK-2 and Bcl-2 might be synchronous and synergistic.
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f6: Up-regulation of KLK10 negatively regulates Bcl-2 and HK-2 expression.(A) CCK-8 cell proliferation assay showed that cell proliferation significantly increased in the Bcl-2- or HK-2-over-expressing PC3-KLK10 cell line compared with the PC3-KLK10 empty vector transfecting cell line (P < 0.001). (B) In the Bcl-2-over-expressing PC3-KLK10 cell line, the expression levels of both HK-2 and KLK10 increased. (C) In the HK-2-over-expressing PC3-KLK10 cell line, the expression levels of Bcl-2 and KLK10 also significantly increased. (D) Potential relationship diagram of KLK10, Bcl-2 and HK-2: the up-regulation of KLK10 might negatively regulate Bcl-2 and HK-2 expression; the expression of HK-2 and Bcl-2 might be synchronous and synergistic.

Mentions: In our study, by introducing the exogenous KLK10 gene into the PC3 cell line, which demonstrated loss of KLK10 mRNA and protein expression, we observed the deceleration of PC3 cell proliferation, apoptotic induction and glucose metabolism reduction. At the molecular level, up-regulated KLK10 expression was accompanied with down-regulated expression of Bcl-2 and HK-2 mRNA and proteins. These results indicated the anticancer role of the KLK10 gene and the potential relationship among KLK10, Bcl-2 and HK-2. In the PC3-KLK10 cell line, Bcl-2 and HK-2 proteins were both down-regulated compared with those in the PC3-Vector cell line. To investigate whether the down-regulation of Bcl-2 and HK-2, which was caused by the up-regulation of KLK10, decelerates PC3 cell proliferation, we up-regulated the Bcl-2 and HK-2 genes, respectively, in the PC3-KLK10 cell line. In the Bcl-2 or HK-2 over-expressed PC3-KLK10 cell lines, cell proliferation was significantly increased compared with the PC3-KLK10 empty vector transfecting cell line (Fig. 6A). Thus, PC3 cell proliferative ability could be recovered via up-regulation of Bcl-2 or HK-2 in the exogenously KLK10 over-expressed PC3 cell line. In the Bcl-2 over-expressed PC3-KLK10 cell line, the expression levels of HK-2 and KLK10 both increased (Fig. 6B). In the HK-2 over-expressed PC3-KLK10 cell line, the expression levels of Bcl-2 and KLK10 also significantly increased (Fig. 6C).


NES1/KLK10 gene represses proliferation, enhances apoptosis and down-regulates glucose metabolism of PC3 prostate cancer cells.

Hu J, Lei H, Fei X, Liang S, Xu H, Qin D, Wang Y, Wu Y, Li B - Sci Rep (2015)

Up-regulation of KLK10 negatively regulates Bcl-2 and HK-2 expression.(A) CCK-8 cell proliferation assay showed that cell proliferation significantly increased in the Bcl-2- or HK-2-over-expressing PC3-KLK10 cell line compared with the PC3-KLK10 empty vector transfecting cell line (P < 0.001). (B) In the Bcl-2-over-expressing PC3-KLK10 cell line, the expression levels of both HK-2 and KLK10 increased. (C) In the HK-2-over-expressing PC3-KLK10 cell line, the expression levels of Bcl-2 and KLK10 also significantly increased. (D) Potential relationship diagram of KLK10, Bcl-2 and HK-2: the up-regulation of KLK10 might negatively regulate Bcl-2 and HK-2 expression; the expression of HK-2 and Bcl-2 might be synchronous and synergistic.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4663538&req=5

f6: Up-regulation of KLK10 negatively regulates Bcl-2 and HK-2 expression.(A) CCK-8 cell proliferation assay showed that cell proliferation significantly increased in the Bcl-2- or HK-2-over-expressing PC3-KLK10 cell line compared with the PC3-KLK10 empty vector transfecting cell line (P < 0.001). (B) In the Bcl-2-over-expressing PC3-KLK10 cell line, the expression levels of both HK-2 and KLK10 increased. (C) In the HK-2-over-expressing PC3-KLK10 cell line, the expression levels of Bcl-2 and KLK10 also significantly increased. (D) Potential relationship diagram of KLK10, Bcl-2 and HK-2: the up-regulation of KLK10 might negatively regulate Bcl-2 and HK-2 expression; the expression of HK-2 and Bcl-2 might be synchronous and synergistic.
Mentions: In our study, by introducing the exogenous KLK10 gene into the PC3 cell line, which demonstrated loss of KLK10 mRNA and protein expression, we observed the deceleration of PC3 cell proliferation, apoptotic induction and glucose metabolism reduction. At the molecular level, up-regulated KLK10 expression was accompanied with down-regulated expression of Bcl-2 and HK-2 mRNA and proteins. These results indicated the anticancer role of the KLK10 gene and the potential relationship among KLK10, Bcl-2 and HK-2. In the PC3-KLK10 cell line, Bcl-2 and HK-2 proteins were both down-regulated compared with those in the PC3-Vector cell line. To investigate whether the down-regulation of Bcl-2 and HK-2, which was caused by the up-regulation of KLK10, decelerates PC3 cell proliferation, we up-regulated the Bcl-2 and HK-2 genes, respectively, in the PC3-KLK10 cell line. In the Bcl-2 or HK-2 over-expressed PC3-KLK10 cell lines, cell proliferation was significantly increased compared with the PC3-KLK10 empty vector transfecting cell line (Fig. 6A). Thus, PC3 cell proliferative ability could be recovered via up-regulation of Bcl-2 or HK-2 in the exogenously KLK10 over-expressed PC3 cell line. In the Bcl-2 over-expressed PC3-KLK10 cell line, the expression levels of HK-2 and KLK10 both increased (Fig. 6B). In the HK-2 over-expressed PC3-KLK10 cell line, the expression levels of Bcl-2 and KLK10 also significantly increased (Fig. 6C).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Rui jin Hospital, School of Medicine, Shanghai JiaoTong University; 197 Ruijin Second Road, Shanghai 200025, China.

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.

No MeSH data available.


Related in: MedlinePlus