Phosphorylation Status of Fas-Associated Death Domain-Containing Protein Regulates Telomerase Activity and Strongly Correlates with Prostate Cancer Outcomes
Phosphorylation Status of Fas-Associated Death Domain-Containing Protein Regulates Telomerase Activity and Strongly Correlates with Prostate Cancer Outcomes
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DOI：
10.1159/000245895
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发表时间：
2009-01-01
期刊：
影响因子：
5
通讯作者：
Konishi, Noboru
中科院分区：
文献类型：
--
作者：
Matsumura, Yoshiaki;Shimada, Keiji;Konishi, Noboru
目的：我们使用前列腺癌细胞系和接受新辅助激素治疗 (NHT) 患者的根治性前列腺切除术样本，研究了丝氨酸 194 处的磷酸化 Fas 相关死亡结构域蛋白 (FADD) 是否调节人端粒酶逆转录酶 (hTERT) 表达、端粒酶活性和癌症进展。方法：我们分析了过表达野生型或突变型 FADD（S194D 或 A）的前列腺癌细胞系中的 hTERT 表达、端粒酶活性和侵袭能力。使用 50 个前列腺切除样本，对 NHT 后活前列腺癌细胞中的 FADD、磷酸化 FADD (p-FADD) 和 hTERT 表达进行免疫组织化学检查。结果：去磷酸化 FADD (S194A) 过表达增强了 hTERT 表达和端粒酶活性，导致细胞增殖和侵袭能力增加。在Kaplan-Meier生存分析中，表达低水平p-FADD和高水平hTERT的前列腺癌患者的生化复发率显着高于高p-FADD和低hTERT表达的患者（p < 0.001）。结论：FADD 在丝氨酸 194 处的磷酸化状态可以通过调节 hTERT 表达和端粒酶活性强烈影响前列腺癌细胞的存活和侵袭。 p-FADD 和 hTERT 表达可能有潜力作为预测 NHT 后生化复发的新生物标志物。版权所有 (C) 2009 S. Karger AG，巴塞尔
Objectives: We investigated whether the phosphorylated Fas-associated death domain protein (FADD) at serine 194 regulated human telomerase reverse transcriptase (hTERT) expression, telomerase activity and cancer progression using prostate cancer cell lines and radical prostatectomy samples taken from patients receiving neoadjuvant hormonal therapy (NHT). Methods: We analyzed hTERT expression, telomerase activity and invasion capacity in prostate cancer cell lines overexpressing the wild-type or mutant form of FADD (S194D or A). FADD, phosphorylated FADD (p-FADD) and hTERT expression in viable prostate cancer cells following NHT were immunohistochemically examined using 50 prostatectomy samples. Results: Dephosphorylated FADD (S194A) overexpression enhanced hTERT expression and telomerase activity, resulting in increased cell proliferation and invasion capacity. In Kaplan-Meier survival analysis, the patients with prostate cancer expressing low levels of p-FADD and high levels of hTERT had significantly higher rates of biochemical recurrence than those with high p-FADD and low hTERT expression (p < 0.001). Conclusions: The phosphorylation status of FADD at serine 194 could strongly affect survival and invasion of prostate cancer cells via modulation of hTERT expression and telomerase activity. p-FADD and hTERT expression may have potential as new biomarkers predicting the biochemical recurrence after NHT. Copyright (C) 2009 S. Karger AG, Basel