Characterization of androgen receptor and nuclear receptor co-regulator expression in human breast cancer cell lines exhibiting differential regulation of kallikreins 2 and 3
Characterization of androgen receptor and nuclear receptor co-regulator expression in human breast cancer cell lines exhibiting differential regulation of kallikreins 2 and 3
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DOI：
10.1002/ijc.10520
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发表时间：
2002-08-10
影响因子：
6.4
通讯作者：
Diamandis, EP
中科院分区：
文献类型：
--
作者：
Magklara, A;Brown, TJ;Diamandis, EP
越来越多的证据表明雄激素和雄激素受体调节乳腺癌的发生和进展；然而，确切的作用和行动仍然不明确。我们之前检查了 BT-474、T-47D、ZR75-1、MCF-7、MFM-223 和 BT-20 人乳腺癌细胞中 2 种已知雄激素调节的激肽释放酶 KLK3（编码 PSA）和 KLK2（编码人激肽释放酶 2 或 hK2）的类固醇激素调节，发现它们受到差异性调节，细胞对 雄激素。为了确定这种可变反应是否由雄激素受体的差异反映出来，我们通过蛋白质印迹分析和饱和结合分析来表征这些细胞中雄激素受体的表达。此外，我们对每个细胞系的雄激素受体 cDNA 进行了测序，以检查是否存在任何雄激素受体突变。通过半定量 RT-PCR 比较这些细胞系中 I1 核受体共调节因子（SRC-1、AIB1、ARA24、ARA54、ARA55、ARA70、ARA160、FHL2、PDEF、NCoR1、SMRT）的表达，以确定这些细胞中表达的受体共激活子或阻遏物的模式是否可以解释 KLK2 和 KLK3。不同细胞系的雄激素受体水平有所不同，但与之前测定的 hK2 和 PSA 分泌无关。没有检测到受体编码区内的突变。除MCF-7细胞表达的受体外，多态性CAG重复长度均在正常范围内。每个乳腺癌细胞系都表现出核受体辅助调节子的独特表达模式，这增加了这些辅助激活子/抑制子的相对水平可能差异调节这些细胞的 KLK2 和 KLK3 启动子/增强子区域内雄激素受体转录活性的可能性。 (C) 2002 Wiley-Liss, Inc.
Accumulating evidence indicates that androgens and the androgen receptor modulate the development and progression of breast adenocarcinoma; however, the precise role and actions remain poorly defined. We examined previously the steroid hormone regulation of 2 known androgen-regulated kallikreins, KLK3 (encoding PSA) and KLK2 (encoding human kallikrein 2 or hK2) in BT-474, T-47D, ZR75-1, MCF-7, MFM-223 and BT-20 human breast cancer cells and found that they were differentially regulated, with the cells showing variable responses to androgen. To determine if this variable response was reflected by differences in androgen receptor, we characterized the expression of androgen receptor in these cells by Western blot analysis and saturation binding analysis. In addition, we sequenced androgen receptor cDNA from each of these cell lines to check whether any androgen receptor mutations were present. The expression of I I nuclear receptor co-regulatory factors (SRC-1, AIB1, ARA24, ARA54, ARA55, ARA70, ARA160, FHL2, PDEF, NCoR1, SMRT) was compared in these cell lines by semi-quantitative RT-PCR to determine if the pattern of receptor co-activators or -repressors expressed in these cells might explain the differential regulation of KLK2 and KLK3. The levels of androgen receptor varied among the cell lines, but did not correlate with hK2 and PSA secretion determined previously. No mutations within the coding regions of the receptor were detected. With the exception of receptor expressed by MCF-7 cells, the polymorphic CAG repeat length was in the normal range. Every breast cancer cell line exhibited a distinct expression pattern of the nuclear receptor co-regulators examined raising the possibility that the relative levels of these co-activators/-repressors might differentially modulate androgen receptor transcriptional activity within the promoter/enhancer region of KLK2 and KLK3 of these cells. (C) 2002 Wiley-Liss, Inc.