Expression and Function of ATIP/MTUSI in Human Prostate Cancer Cell Lines
Expression and Function of ATIP/MTUSI in Human Prostate Cancer Cell Lines
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DOI：
10.1002/pros.21192
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发表时间：
2010-10-01
期刊：
影响因子：
2.8
通讯作者：
Louis, William J.
中科院分区：
文献类型：
--
作者：
Louis, Simon N. S.;Chow, Laurie;Louis, William J.
背景。我们之前已经证明，Ang II 2 型 (AT(2)-) 受体介导的对雄激素依赖性 (LNCaP) 和独立 (PC3) 前列腺癌细胞系中 EGF 诱导的前列腺癌细胞生长的抑制作用。为了探索参与这种抑制作用的信号通路，我们使用实时 PCR、过表达、siRNA 和 [(3)H] 胸苷掺入分析检测了 AT(2) 受体与其新型调节伙伴 ATIP 的相互作用。结果。人类前列腺癌细胞系的结果表明，在所检测的两种细胞系中都存在 ATIP，并表明 (i) AT(2)-受体通过与 ATIP 相互作用在雄激素依赖性和雄激素非依赖性细胞系中介导抗生长因子作用； (ii) ATIP 表达随着细胞生长速率和雄激素非依赖性的增加而降低； (iii) EGF 可能部分通过降低细胞中 ATIP 的含量来作用于细胞生长。结论。结果支持我们之前在正常细胞系中提出的观点，即 ATIP 是细胞对 AT(2) 受体激活反应的重要组成部分。结果进一步表明，需要关键水平的ATIP来介导AT(2)受体激活的作用，从而抑制EGF介导的细胞生长增加。他们还表明，EGF 可能通过抑制 ATIP 表达水平来部分诱导细胞生长。前列腺 70：1563-1574，2010。(C) 2010 Wiley-Liss, Inc.
BACKGROUND. We have previously demonstrated Ang II type 2 (AT(2)-) receptor-mediated inhibition of EGF-induced prostate cancer cell growth in androgen-dependent (LNCaP) and independent (PC3) prostate cancer cell lines.METHODS. To explore the signaling pathways involved in this inhibitory effect, we examined the interaction of the AT(2)-receptor with its novel regulatory partner ATIP using real time PCR, over-expression, siRNA and [(3)H] thymidine incorporation assays.RESULTS. The results in human prostate cancer cell lines demonstrate the presence of ATIP in both cell lines examined, and suggest that (i) the AT(2)-receptor through an interaction with ATIP mediates an anti-growth factor effect in both androgen-dependent and androgen-independent cell lines; (ii) ATIP expression decreases as the rate of cell growth and androgen-independence increase; and (iii) EGF may act on cell growth in part by reducing the content of ATIP present in the cells.CONCLUSIONS. The results support our earlier proposal in normal cell lines that ATIP is an important component of the cellular response to AT(2)-receptor activation. The results further suggest that a critical level of ATIP is required to mediate the effect of AT(2)-receptor activation to inhibit EGF mediated increases in cell growth. They also suggest that EGF may in part induce cell growth by suppressing the level of ATIP expression. Prostate 70: 1563-1574, 2010. (C) 2010 Wiley-Liss, Inc.