Impact of BCL2 Overexpression in castration resistance prostate cancer progression I

In analyzing transcriptomic data from a clinical trial of neoadjuvant-intensive Androgen Deprivation Therapy, we observed increased mRNA expression of the hallmark antiapoptotic gene BCL2 in the prostate tumors of treated patients versus those of untreated patients. We showed that BCL2 overexpressed LNCaP cells exhibited resistance to prolonged androgen deprivation therapy, indicating that BCL2-overexpression leads to castration resistance and cellular plasticity.Our study indicating that BCL2 overexpression may act as a major driver of early castration resistance in prostate cancer cells. To investigate the function of BCL2, we stably overexpressed humna BCL2 in prostate cancer cells. We grow the isogenic pairs of cells to androgen deprivation for a prolonged time (28 days) and perfermed RNA sequencing

在对新辅助强化雄激素剥夺治疗（Androgen Deprivation Therapy，ADT）临床试验的转录组数据进行分析时，我们观察到，与未接受治疗的患者相比，接受治疗的患者前列腺肿瘤中标志性抗凋亡基因BCL2的mRNA表达水平显著升高。我们证实，过表达BCL2的LNCaP细胞对长期雄激素剥夺治疗产生耐药性，这表明BCL2过表达可引发去势抵抗与细胞可塑性。本研究提示，BCL2过表达可能是前列腺癌细胞早期去势抵抗的核心驱动因素。为探究BCL2的功能，我们在前列腺癌细胞中稳定过表达人源BCL2基因。我们将同基因配对细胞系置于长期（28天）雄激素剥夺条件下培养，并进行了RNA测序。