Jiang Feng, Wang Zhou
Department of Urology, Northwestern University, Chicago, Illinois, USA.
Prostate. 2004 Jun 1;59(4):426-35. doi: 10.1002/pros.20000.
Promyelocytic leukemia zinc finger protein (PLZF) was initially identified by virtue of its fusion with RARalpha as a result of a variant t(11;17) chromosomal translocation that occurs in a small subset of acute promyelocytic leukemia (APL) patients. PLZF has been reported to have pro-apoptotic and anti-proliferative activity both in vivo and in vitro.
Using a modified subtractive hybridization, we identified PLZF as an androgen-responsive gene in the rat ventral prostate. Northern blot and Western blot were used to characterize the regulation of PLZF by androgens in LNCaP cells. Stable transfections of PLZF in LNCaP cells were performed to assay the effect of PLZF overexpression on LNCaP cell proliferation.
PLZF mRNA was transiently up-regulated by androgens in the regressed ventral prostate of castrated adult rat. PLZF was also up-regulated by androgens, at both mRNA and protein levels, in the androgen-responsive human prostate cancer cell line LNCaP. Androgen induction of PLZF mRNA was not inhibited by protein synthesis inhibitor cycloheximide but inhibited by androgen receptor antagonist bicalutamide, indicating that PLZF is a direct androgen-responsive gene. To study the functions of PLZF in androgen action, LNCaP sublines stably overexpressing PLZF were generated. PLZF overexpression inhibited LNCaP proliferation either in the presence or absence of androgen, which is consistent with the reported anti-proliferative activity of PLZF.
The above observations indicate that PLZF is an androgen-responsive gene with anti-proliferative activity in prostate cancer cells.
早幼粒细胞白血病锌指蛋白（PLZF）最初是因其与RARα融合而被鉴定出来的，这种融合是由一小部分急性早幼粒细胞白血病（APL）患者中发生的变异t(11;17)染色体易位导致的。据报道，PLZF在体内和体外均具有促凋亡和抗增殖活性。
我们采用改良的消减杂交技术，将PLZF鉴定为大鼠腹侧前列腺中的雄激素反应基因。运用Northern印迹法和Western印迹法来表征雄激素对LNCaP细胞中PLZF的调控作用。在LNCaP细胞中进行PLZF的稳定转染，以检测PLZF过表达对LNCaP细胞增殖的影响。
在去势成年大鼠退化的腹侧前列腺中，PLZF mRNA被雄激素短暂上调。在雄激素反应性人前列腺癌细胞系LNCaP中，PLZF在mRNA和蛋白质水平上也被雄激素上调。蛋白质合成抑制剂环己酰亚胺不会抑制雄激素对PLZF mRNA的诱导作用，但雄激素受体拮抗剂比卡鲁胺会抑制这种诱导作用，这表明PLZF是一个直接的雄激素反应基因。为了研究PLZF在雄激素作用中的功能，构建了稳定过表达PLZF的LNCaP亚系。无论有无雄激素存在，PLZF过表达均抑制LNCaP的增殖，这与报道的PLZF的抗增殖活性一致。
上述观察结果表明，PLZF是一种在前列腺癌细胞中具有抗增殖活性的雄激素反应基因。
