Effect And Mechanism Of Egr1 On Androgen Deprivation Of Prostate Cancer Cell

Background:Prostate carcinoma (PCa) is one of the most common malignances in United States and Europe, which was the second cause for males death. Although the incidence of prostate cancer was low in our country, but in recently years confirmed PCa is getting higher and higher in China today with the aging and the diet habit changing. Androgen deprivation therapy (ADT) is generally employed for the treatment of advanced or metastatic prostate cancer, because the growth and progression of prostate cancer are initially androgen-dependent. However, the prostate cancer eventually progresses from an androgen-dependent to an aggressive androgen-independent stage, when it shows poor response to any anti-cancer therapy. It is not clear the mechanism of AIPC informed.It is lack of effective treatment when the prostate cancer change to androgen-independent prostate cancer. The patient's prognosis is poor, when radiation and chemotherapy is applied.The early growth response gene 1 (Egr1) is a zinc finger transcription factor that belongs to a multigene family that includes Egr2, Egr3, Egr4. This is significant and specific to prostate tumor cells because in mammary, lung and glial tumors, Egr1, is not over-expressed but is low or absent. Egr1 is overexpressed in human prostate tumors but is low in or absent from normal prostate tissue. The level of Egr1 expression was found be correlated with PCa malignancy, progression, metastasis and prognosis. It was found that overexpression of Egr1 could be upregulated insulin-like growth factor-Ⅱ, transforming growth factor-β1 and platelet-derived growth factor-A.Egr1 was so very important in PCa informed, it maybe also play important role in androgen-independ prostate cancer informed. Id-1 was contribute to androgen-independ prostate cancer informed. Was overexpression Egr1 will upregulated Id1 expression,or Egrl protein may serve as an important molecular marker of androgen independent progression of PCa.Objective:The mechanism of Egr1 in the androgen-independent prostate cancer formation, the relationship between the androgen receptor and Egr1. Egr1 could be promote androgen-dependent prostate cancer changed to androgen-independent transformation mediated through Id.Methods:Expression of Egr1 were compared in 24 cases of androgen-dependent prostate cancer and 5 cases of androgen-independent prostate cancer. In vitro to mime of the clinical treatment for prostate cancer, the level of Egrl were observed in androgen deprivation in prostate cancer cells. Prostate cancer cells were treated by dihydrotestosterone and flutamide, the level of Egr1 were observed. Repeat the above experiment when PC3 transfected with androgen receptor. The level of Egr1 and Id1 were observation when prostate cancer cells were treated with Bombesin. The trend of Egr1 and Id were observed among different Gleason score in 24 cases of androgen-dependent prostate cancer.Results:1.24 cases of androgen-dependent prostate cancer and 5 cases of androgen-independent prostate cancer were compared. Five cases of androgen-independent prostate cancer were strongly positive (+++), from 24 cases androgen-dependent prostate cancer,11 cases of weak positive of (+),9 cases were positive (++),4 cases of strong positive (+++) (P=0.003).2. Egr1 in PC3 cells was about 54 times than LNCaP cells, which was consisted with Westblot result. Prostate cancer cell line LNCaP and PC3 cells were under androgen deprivation for 1-4 days in vitro. Egr1 level was increased after androgen deprivation in the mRNA and protein levels in LNCaP cell lines. Egr1 level was no significant change after androgen deprivation in the mRNA and protein levels in PC3 cell line.3. In androgen sensitive LNCaP cells which contained androgen receptor, dihydrotestosterone inhibited Egr1 expression, while flutamide increased Egr1 expression, both in a dose-dependent manner. While no statistically significant difference was found in Egr1 expression in AR-negative PC-3 cells in the same circumstance. When androgen receptor was introduced into PC-3 cells, PC3 was showed the same phenomenon during dihydrotestosterone and flutamide used as found in LNCaP.4. Bombesin (Bombesin, Egr1 agonist) can be significantly up-regulated Egr1 and Id1 expression in mRNA level and protein level in LNCaP and PC3 cells in a dose-dependent manner. In the 24 cases of prostate cancer tissue samples, according to Gleason score were divided into three groups (group A<7, group B=7, group C>7), in which A group and C group between Egr1 and Id1 differences in statistical significance (Egr1 P=0.025, Id1 P=0.005)。Conclusion:Egr1 was significantly higher expression in androgen-independent prostate cancer. In the androgen-dependent prostate cancer, Egr1 expression was gradually increased after androgen deprivation. Egr1 expression in androgen dependent prostate cancer was negatively regulated by androgen in a receptor-dependent way. Increased Egr1 was mediated high expression of Id1 after androgen deprivation, which might contribute to emergence of androgen- independend prostate cancer.