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.
Highlights
As an androgen-independent prostate cancer cell line, the PC3 cell line was investigated for KLK10 function in prostate cancer
Our functional studies confirmed the important role of the KLK10 gene in the tumour suppression of the KLK10-deficient, androgen-independent prostate cancer cell line PC3
The exogenous over-expression of KLK10 in PC3 cells could decelerate tumour proliferation, which is accompanied by apoptosis induction and glucose metabolism reduction
Summary
NES1 cDNA was revealed as a novel serine protease with high homology to the glandular kallikrein family[7], and the localisation of the NES1 gene is shown on chromosome 19q13.4, a locus where most kallikreins are located[8,9] Based on these characteristics, the NES1 gene is designated as KLK10, a member of the kallikrein family, and its encoded protein is human kallikrein 10 (hK10)[10]. We confirmed that the expression of KLK10 was low in prostate cancer tissue and cell lines, including LNCaP clone FGC and PC3. Both have been widely utilised as cell models for prostate cancer studies and are generally assumed to represent early and late stages of prostate cancer, respectively[15]. Considering the androgen-independent growth characteristics of the PC3 cell line, it was chosen in our study as an advanced prostate cancer model to investigate the effect of KLK10 on cancer proliferation, apoptosis and glucose metabolism
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
