title: Androgen deprivation therapy induces androgen receptor-dependent upregulation of Egr1 in prostate cancers.
abstract: Early growth response gene-1 (Egr1) has a crucial function in the development and progression of prostate cancer. However, whether Egr1 contributes to the transition of advanced androgen-independent prostate cancer (AIPC) from androgen-dependent prostate cancer (ADPC) remains largely unknown. To the best of our knowledge, through immunohistochemical staining methods, we were the first to identify that Egr1 is more highly expressed in AIPC clinical specimens than in androgen-dependent prostate cancer (ADPC). An in vitro study with quantitative RT-PCR and Western blot demonstrated that Egr1 also has a higher expression in androgen-independent PC3 cells than in the androgen-dependent LNCaP cells. Egr1 expression in LNCaP cells was significantly upregulated during the androgen deprivation treatment (ADT) and was re-downregulated through the addition of dihydrotestosterone. Although no variation in PC3 cells was identified, Egr1 responded to dihydrotestosterone and flutamide in the androgen receptor (AR)-transfected PC3 cells. Further investigation with Egr1 agonist and specific siRNA-targeting Egr1 revealed that Egr1 upregulation or downregulation was accompanied by a change in inhibitors of differentiation and DNA binding-1 (Id1) in the same direction in both LNCaP and PC3 cells. The variation is shown to be negatively regulated by androgen through AR during ADT. Our data suggested that upregulated Egr1 might partially contribute to the emergence of AIPC after prolonged ADT. This study also elucidated the potential mechanism underlying Id1 participation in the progression of prostate cancer. Understanding the key molecular events in the transition from ADPC to AIPC may provide new therapeutic intervention strategies for patients with AIPC.
authors.affiliation: Department of Urology, Changhai Hospital, Second Military Medical University Shanghai 200433, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Hematology, Changhai Hospital, Second Military Medical University Shanghai 200433, China.
authors.forename: Gusheng
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Urology, Changhai Hospital, Second Military Medical University Shanghai 200433, China.
authors.forename: Chengwu
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Urology, Changhai Hospital, Second Military Medical University Shanghai 200433, China.
authors.forename: Linhui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, Changhai Hospital, Second Military Medical University Shanghai 200433, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Urology, Changhai Hospital, Second Military Medical University Shanghai 200433, China.
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018450:Disease Progression; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D034741:RNA, Small Interfering; D011944:Receptors, Androgen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
chemical_list: C410798:AR protein, human; D018931:Antineoplastic Agents, Hormonal; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D034741:RNA, Small Interfering; D011944:Receptors, Androgen
keywords: Egr1; Id1; Prostate cancer; androgen deprivation treatmen; androgen receptor