Expression of receptors for luteinizing hormone-releasing hormone in human ovarian and endometrial cancers: frequency, autoregulation, and correlation with direct antiproliferative activity of luteinizing hormone-releasing hormone analogues.
Expression of receptors for luteinizing hormone-releasing hormone in human ovarian and endometrial cancers: frequency, autoregulation, and correlation with direct antiproliferative activity of luteinizing hormone-releasing hormone analogues.
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DOI：
10.1067/mob.2002.119633
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发表时间：
2002-02
影响因子：
9.8
通讯作者：
P. Völker;C. Gründker;Oswald Schmidt;K. Schulz;G. Emons
中科院分区：
文献类型：
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作者：
P. Völker;C. Gründker;Oswald Schmidt;K. Schulz;G. Emons
目的：近年来的研究表明，促黄体生成素释放激素受体在卵巢癌和子宫内膜癌中有表达。争议持续存在的相关性，这一发现，特别是是否这些受体介导的促黄体生成素释放激素类似物的直接抗增殖作用。我们将特征明确的卵巢癌和子宫内膜癌细胞系的促黄体生成素释放激素受体的表达与促黄体生成素释放激素类似物降低其增殖的能力相关联，并研究促黄体生成素释放激素激动剂曲普瑞林和拮抗剂西曲瑞克对促黄体生成素释放激素受体表达的自动调节。在一系列原发性卵巢癌和子宫内膜癌标本中评估促黄体生成激素释放激素受体的表达。研究设计：用半定量逆转录聚合酶链反应和放射配体结合分析评估促黄体生成素释放激素受体的表达。在不存在或存在促黄体生成素释放激素类似物的情况下，通过增殖测定确定抗增殖作用。结果卵巢癌细胞系（4/6）和子宫内膜癌细胞系（5/6）表达促黄体生成素释放激素受体。这些促黄体生成素释放激素受体阳性细胞系的增殖是剂量和时间依赖性减少激动剂和拮抗剂促黄体生成素释放激素类似物。促黄体生成素释放激素类似物使促黄体生成素释放激素受体密度降低至对照组的80%（对照组，100%; P <0.001）。70%的原发性卵巢癌和83%的原发性子宫内膜癌表达促黄体生成素释放激素受体。结论人卵巢癌和子宫内膜癌细胞表达的促黄体生成素释放激素受体介导促黄体生成素释放激素类似物的直接抗增殖作用。由于大多数原发性癌症表达促黄体生成激素释放激素受体，这些受体可能用于新的抗增殖治疗方法，并应进一步评估。
OBJECTIVE Several recent reports have demonstrated the expression of luteinizing hormone-releasing hormone receptors by human ovarian and endometrial cancers. Controversy persists on the relevance of this finding, in particular whether these receptors mediate direct antiproliferative effects of luteinizing hormone-releasing hormone analogues. We correlated the expression of luteinizing hormone-releasing hormone receptors by well-characterized ovarian and endometrial cancer cell lines with the ability of luteinizing hormone-releasing hormone analogues to reduce their proliferation and studied the autoregulation of luteinizing hormone-releasing hormone receptor expression by luteinizing hormone-releasing hormone agonist triptorelin and antagonist cetrorelix. The expression of luteinizing hormone-releasing hormone receptors was assessed in a series of specimens from primary ovarian and endometrial cancers. STUDY DESIGN Luteinizing hormone-releasing hormone receptor expression was assessed by semiquantitative reverse transcriptase-polymerase chain reaction and radioligand binding assay. Antiproliferative effects were ascertained by proliferation assays in the absence or presence of luteinizing hormone-releasing hormone analogues. RESULTS Ovarian (4/6 cell lines) and endometrial (5/6 cell lines) cancer cell lines expressed luteinizing hormone-releasing hormone receptors. The proliferation of these luteinizing hormone-releasing hormone receptor-positive cell lines was dose- and time-dependently reduced by agonistic and antagonistic luteinizing hormone-releasing hormone analogues. Luteinizing hormone-releasing hormone receptor density was reduced to 80% of controls (control, 100 %; P <.001) by luteinizing hormone-releasing hormone analogues. Seventy percent of primary ovarian cancers and 83% of primary endometrial cancers expressed luteinizing hormone-releasing hormone receptors. CONCLUSION These findings suggest that luteinizing hormone-releasing hormone receptors that are expressed by human ovarian and endometrial cancer cell lines mediate direct antiproliferative effects of luteinizing hormone-releasing hormone analogues. Because most respective primary cancers expressed luteinizing hormone-releasing hormone receptors, these receptors might be used for novel antiproliferative therapeutic approaches and should be further evaluated.