Abstract
Prostate cancer is the second leading cause of morbidity and mortality in males in the Western world. In the present study, LNCaP, which is an androgen receptor-positive and androgen-responsive prostate cancer cell line derived from lymph node metastasis, and DU145, which is an androgen receptor-negative prostate cancer cell line derived from brain metastasis, were investigated. TNFα treatment decreased p105 and p50 expression and R1881 treatment slightly decreased p105 expression but increased p50 expression with or without TNFα induction. As an aggressive prostate cancer cell line, DU145 transfected with six transmembrane protein of prostate (STAMP)1 or STAMP2 was also exposed to TNFα. Western blotting indicated that transfection with either STAMP gene caused a significant increase in NFκB expression following TNFα induction. In addition, following the treatment of LNCaP cells with TNFα, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed with a panel of apoptosis-related gene primers. The apoptosis-related genes p53, p73, caspase 7 and caspase 9 showed statistically significant increases in expression levels while the expression levels of MDM2 and STAMP1 decreased following TNFα induction. Furthermore, LNCaP cells were transfected with a small interfering NFκB (siNFκB) construct for 1 and 4 days and induced with TNFα for the final 24 h. RT-qPCR amplifications were performed with apoptosis-related gene primers, including p53, caspases and STAMPs. However, no changes in the level of STAMP2 were observed between cells in the presence or absence of TNFα induction or between those transfected or not transfected with siNFκB; however, the level of STAMP1 was significantly decreased by TNFα induction, and significantly increased with siNFκB transfection. Silencing of the survival gene NFκB caused anti-apoptotic STAMP1 expression to increase, which repressed p53, together with MDM2. NFκB silencing had varying effects on a panel of cancer regulatory genes. Therefore, the effective inhibition of NFκB may be critical in providing a targeted pathway for prostate cancer prevention.
Highlights
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in males in the Western world
tumor necrosis factor α (TNFα) induction following HisMAX-STAMP1 transfection led to an increase in the expression level of p50
HisMAX‐STAMP2 transfection increased the expression level of p50, and TNFα induction had no effect on the expression level of p50 in cells transfected with HisMAX-STAMP2 (Fig. 2)
Summary
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in males in the Western world. Human prostate adenocarcinoma cell lines are normally resistant to programmed cell death, known as apoptosis [1]. Six transmembrane epithelial antigen of the prostate (STEAP) [2] belongs to the six transmembrane protein of prostate (STAMP) gene family, and is the first characterized transmembrane gene that is enriched in the prostate. Other members of the STAMP family include pHyde, a rat protein that has been implicated in the apoptosis of prostate cancer cells [6], and its human homolog, tumor suppressor-activated pathway 6 (TSAP6), known as STEAP3, a p53‐inducible gene, involved in apoptosis and the cell cycle in prostate cancer and HeLa cells [7]
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