Androgen receptor W741C and T877A mutations in AIDL cells, an androgen-independent subline of prostate cancer LNCaP cells
Androgen receptor W741C and T877A mutations in AIDL cells, an androgen-independent subline of prostate cancer LNCaP cells
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DOI：
10.1007/s13277-011-0209-y
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发表时间：
2011-12-01
期刊：
影响因子：
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通讯作者：
Hirano, Kazuyuki
中科院分区：
文献类型：
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作者：
Otsuka, Takashi;Iguchi, Kazuhiro;Hirano, Kazuyuki
雄激素非依赖性LNCaP（AIDL）细胞系是通过将前列腺癌LNCaP细胞维持在去唾液酸培养基中产生的。值得注意的是，与亲本LNCaP细胞相比，合成雄激素R1881相关的基因应答在AIDL细胞中减弱。本研究的目的是阐明AIDL细胞雄激素敏感性的机制。我们首先检测了雄激素受体（AR）及其辅助调节因子的表达。LNCaP和AIDL细胞的mRNA表达无明显差异。值得注意的是，AR蛋白水平诱导的R1881和DHT在LNCaP细胞，但不是在AIDL细胞。我们接下来进行cDNA测序以检测AR基因中的突变。在LNCaP和AIDL细胞中均检测到T877 A突变。此外，AIDL细胞在AR基因中具有错义取代（TGG -> TGT），这导致密码子741处的点突变（W741 C）。先前已报道双T877 A和W741 C AR突变体表现出降低的雄激素敏感性。因此，AIDL细胞的低雄激素敏感性反应可以至少部分地由AR基因突变来解释。
The androgen-independent LNCaP (AIDL) cell line was generated by maintaining prostate cancer LNCaP cells in a hormone-deprived medium. Notably, synthetic androgen R1881-related gene response is attenuated in AIDL cells as compared to the parental LNCaP cells. The aim of this study was to clarify the mechanisms underlying androgen sensitivity in AIDL cells. We first examined the expression of androgen receptor (AR) and its co-regulators. However, no significant difference in mRNA expression was found between LNCaP and AIDL cells. Remarkably, AR protein levels were induced by R1881 and DHT in LNCaP cells, but not in AIDL cells. We next performed the cDNA sequencing to detect mutations in the AR gene. The T877A mutation was detected both in LNCaP and AIDL cells. Furthermore, AIDL cells harbored a missense substitution (TGG -> TGT) in the AR gene, which caused a point mutation at codon 741 (W741C). Double T877A and W741C AR mutants have been previously reported to exhibit reduced androgen sensitivity. Hence, the low-androgen-sensitive responses of AIDL cells may be explained, at least in part, by AR gene mutations.