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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

Expression of KLK10 is low in prostate cancer tissue and cell lines.(A: I, II) KLK10 protein gains presented nigger-brown and were regularly arranged in the cytoplasm of BPH tissue. (A: III, IV) KLK10 protein gains presented brown and were regularly arranged in the cytoplasm of matched adjacent normal tissue of prostate cancer. (A: V, VI) KLK10 protein grains were lighter or even absent and were irregularly arranged in the cytoplasm of prostate cancer tissue. (B) KLK10 mRNA expression was significantly lower in PC3, DU145 and LNCaP clone FGC than in RWPE-1. (C) KLK10 protein expression was almost lost in PC3, DU145 and LNCaP clone FGC compared with that in RWPE-1.
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f1: Expression of KLK10 is low in prostate cancer tissue and cell lines.(A: I, II) KLK10 protein gains presented nigger-brown and were regularly arranged in the cytoplasm of BPH tissue. (A: III, IV) KLK10 protein gains presented brown and were regularly arranged in the cytoplasm of matched adjacent normal tissue of prostate cancer. (A: V, VI) KLK10 protein grains were lighter or even absent and were irregularly arranged in the cytoplasm of prostate cancer tissue. (B) KLK10 mRNA expression was significantly lower in PC3, DU145 and LNCaP clone FGC than in RWPE-1. (C) KLK10 protein expression was almost lost in PC3, DU145 and LNCaP clone FGC compared with that in RWPE-1.

Mentions: In the tissue of benign prostate hyperblastosis (BPH) (Fig. 1A, I and II) and the matched adjacent normal tissue of prostate cancer (Fig. 1A, III and IV), hK10 presented as brown or dark brown grains in the cytoplasm near the nucleus, mainly facing the side of the acinar lumina. However, in prostate cancer tissue, the expression of hK10 was much lower, which presented as light or absent grains, irregularly arranged in the cytoplasm (Fig. 1A, V and VI). The positive rate of hK10 expression in the cancer tissue of prostate cancer patients was only 38.3% (23/60). By contrast, in the matched adjacent normal tissue of prostate cancer patients and in the tissue of BPH patients, the positive rate was significantly higher (93.33% [56/60] and 100% [20/20]; Pā€‰<ā€‰0.0001, respectively; Table 1).


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)

Expression of KLK10 is low in prostate cancer tissue and cell lines.(A: I, II) KLK10 protein gains presented nigger-brown and were regularly arranged in the cytoplasm of BPH tissue. (A: III, IV) KLK10 protein gains presented brown and were regularly arranged in the cytoplasm of matched adjacent normal tissue of prostate cancer. (A: V, VI) KLK10 protein grains were lighter or even absent and were irregularly arranged in the cytoplasm of prostate cancer tissue. (B) KLK10 mRNA expression was significantly lower in PC3, DU145 and LNCaP clone FGC than in RWPE-1. (C) KLK10 protein expression was almost lost in PC3, DU145 and LNCaP clone FGC compared with that in RWPE-1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Expression of KLK10 is low in prostate cancer tissue and cell lines.(A: I, II) KLK10 protein gains presented nigger-brown and were regularly arranged in the cytoplasm of BPH tissue. (A: III, IV) KLK10 protein gains presented brown and were regularly arranged in the cytoplasm of matched adjacent normal tissue of prostate cancer. (A: V, VI) KLK10 protein grains were lighter or even absent and were irregularly arranged in the cytoplasm of prostate cancer tissue. (B) KLK10 mRNA expression was significantly lower in PC3, DU145 and LNCaP clone FGC than in RWPE-1. (C) KLK10 protein expression was almost lost in PC3, DU145 and LNCaP clone FGC compared with that in RWPE-1.
Mentions: In the tissue of benign prostate hyperblastosis (BPH) (Fig. 1A, I and II) and the matched adjacent normal tissue of prostate cancer (Fig. 1A, III and IV), hK10 presented as brown or dark brown grains in the cytoplasm near the nucleus, mainly facing the side of the acinar lumina. However, in prostate cancer tissue, the expression of hK10 was much lower, which presented as light or absent grains, irregularly arranged in the cytoplasm (Fig. 1A, V and VI). The positive rate of hK10 expression in the cancer tissue of prostate cancer patients was only 38.3% (23/60). By contrast, in the matched adjacent normal tissue of prostate cancer patients and in the tissue of BPH patients, the positive rate was significantly higher (93.33% [56/60] and 100% [20/20]; Pā€‰<ā€‰0.0001, respectively; Table 1).

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