Malinowska Kamilla, Cavarretta Ilaria T, Susani Martin, Wrulich Oliver A, Uberall Florian, Kenner Lukas, Culig Zoran
Department of Urology and Biocenter, Innsbruck Medical University, Innsbruck, Austria.
Prostate. 2009 Jul 1;69(10):1109-18. doi: 10.1002/pros.20956.
Androgen receptor (AR) signaling is implicated in prostate cancer progression. Therefore, identification of AR downstream genes is potentially important for selection of novel markers and therapy targets in prostate cancer.
Expression of a thyroid hormone T3-binding protein mu-crystallin (CRYM) mRNA and protein in cell lines was evaluated by real-time PCR and Western blot, respectively. CRYM expression in vivo was analyzed in patients' samples by immunohistochemistry. The effects of androgen and T3 on proliferation of MDA PCa 2b cells were assessed by (3)H-thymidine uptake assay.
CRYM expression was detected in AR-positive LNCaP and MDA PCa 2b cells. In MDA PCA 2b cells, CRYM was regulated by androgens. Androgen-induced CRYM expression was diminished by antiandrogens or AR siRNA. Inhibition of transcription by alpha-amanitin caused a reduction in CRYM mRNA. The lack of CRYM expression was noted in LAPC-4 cells and in AR-negative prostate cancer cell lines PC-3 and DU-145. CRYM protein was increased in cancer tissue and decreased in samples from patients after hormonal therapy. In samples from patients with therapy-refractory cancer CRYM was not detectable. We also found that androgens and T3 have additive effects on stimulation of MDA PCa 2b cells proliferation.
CRYM is a novel androgen-regulated gene whose expression is elevated in prostate cancer but down-regulated in castration therapy-resistant tumors.
雄激素受体（AR）信号传导与前列腺癌进展有关。因此，鉴定AR下游基因对于前列腺癌新标志物和治疗靶点的选择可能具有重要意义。
分别通过实时PCR和蛋白质印迹法评估细胞系中甲状腺激素T3结合蛋白μ-晶状体蛋白（CRYM）mRNA和蛋白质的表达。通过免疫组织化学分析患者样本中CRYM在体内的表达。通过³H-胸腺嘧啶摄取试验评估雄激素和T3对MDA PCa 2b细胞增殖的影响。
在AR阳性的LNCaP和MDA PCa 2b细胞中检测到CRYM表达。在MDA PCA 2b细胞中，CRYM受雄激素调节。抗雄激素或AR siRNA可减少雄激素诱导的CRYM表达。α-鹅膏蕈碱抑制转录导致CRYM mRNA减少。在LAPC-4细胞以及AR阴性前列腺癌细胞系PC-3和DU-145中未检测到CRYM表达。CRYM蛋白在癌组织中增加，而在接受激素治疗的患者样本中减少。在治疗难治性癌症患者的样本中未检测到CRYM。我们还发现雄激素和T3对MDA PCa 2b细胞增殖的刺激具有相加作用。
CRYM是一种新的雄激素调节基因，其表达在前列腺癌中升高，但在去势治疗耐药肿瘤中下调。
