Expression And Significance Of FKBP5in Androgen-independent Prostate Cancer

Objective:Detection the expression of FKBP5in androgen-dependent, castrated3days and androgen-independent prostate orthotopic tumor tissue and the expression of FKBP5in androgen-dependent and androgen-independent human prostate cancer tissues,to explore the change mechanism of androgen-dependent to androgen-independent prostate cancer and the clinical significance of FKBP5on the treatment androgen-independent prostate cancer.Methods:Using established androgen-independent prostate orthotopic tumor model in nude mice using LNCaP cells,select the androgen-dependent, castrated3days and androgen-independent prostate orthotopic tumor tissue. Finding different gene by Gene chip, RT-PCR, Real-time qPCR were used to detect the gene expression of FKBP5in three tumor tissues. Immunohistochemical method was used to detect the protein expression of FKBP5in three tumor tissues and human benign prostate hyperplasia,androgen-dependent prostate cancer, androgen deprivation therapy prostate cancer and androgen-independent prostate cancer tissues. Statistical method was used to analysis the FKBP5expression differences in three tumor tissues and human benign prostate hyperplasia,androgen-dependent prostate cancer, androgen deprivation therapy prostate cancer and androgen-independent prostate cancer tissues.Results:1. Gene Chip:FKBP5gene in androgen-independent tumor tissues was significantly higher than androgen-dependent and castrated3days tumor tissues and castrated3days tumor tissues was slightly lower than androgen-dependent tumor tissues(androgen-dependent tumor tissues:castrated3days tumor tissues: androgen-independent tumor tissues-1:0.62:4.5).2. RT-PCR:1) Androgen-dependent tumor tissues FKBP5mRNA expression was lower than the castrated3days tumor tissues.And there was significant difference (P <0.05).2) Androgen-independent tumor tissues FKBP5mRNA expression was higher than the androgen-dependent tumor tissues. And there was significant difference (P <0.05).3) Androgen-independent tumor tissues FKBP5mRNA expression was higher than the castrated3days tumor tissues.And there was significant difference (P<0.05). 3.Real-time qPCR:FKBP5gene in androgen-independent tumor tissues was significantly higher than androgen-dependent and castrated3days tumor tissues and castrated3days tumor tissues was slightly higher than androgen-dependent tumor tissues(androgen-dependent tumor tissuesrcastrated3days tumor tissues: androgen-independent tumor tissues=1:1.8:6.3).4.Animal models immunohistochemistry:1) Androgen-dependent tumor tissues and castrated3days tumor tissues FKBP5protein expression was small different. And there was no significant difference (P>0.05).2) Androgen-independent tumor tissues FKBP5protein expression was higher than androgen-dependent tumor tissues. And there was significant difference(P<0.05).3) Androgen-independent tumor tissues FKBP5protein expression was higher than castrated3days tumor tissues. And there was significant difference(P<0.05).5.Human tissues immunohistochemistry:1)human androgen-independent prostate cancer tissues FKBP5protein expression was higher than benign prostate hyperplasia tissues. And there was significant difference (P<0.05).2)human androgen-independent prostate cancer tissues FKBP5protein expression was higher than androgen deprivation therapy prostate cancer tissues. And there was significant difference (P<0.05).3)human androgen-independent prostate cancer tissues FKBP5protein expression was lower than androgen-independent prostate cancer tissues. And there was significant difference (P<0.05).Conclusions:1.FKBP5is overexpressed in androgen-independent prostate orthotopic tumor model in nude mice using LNCaP cells. FKBP5plays an important role in the androgen-independent prostate cancer transformation process, which may be related to the role of androgen receptor signaling pathway or other signaling pathway.2. FKBP5is overexpressed in human androgen-independent prostate cancer tissues. FKBP5inhibitor FK506has some clinical significance for the treatment of prostate cancer and open up new prostate cancer therapeutic areas especially for androgen-independent prostate cancer.