Fekete M, Wittliff J L, Schally A V
Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, Louisiana.
J Clin Lab Anal. 1989;3(3):137-47. doi: 10.1002/jcla.1860030302.
Binding capacities and apparent dissociation constants of receptors for [D-Trp6]-luteinizing hormone-releasing hormone [( D-Trp6]-LH-RH), somatostatin (SS-14), epidermal growth factor (EGF), and estrogen and progesterone were determined in 500 breast cancer specimens using multipoint assays. Specific binding sites greater than 10 fmol/mg cytosol protein for estrogen were found in 408 carcinomas (81.6%), and for progesterone in 340 specimens (68%). High affinity EGF receptors were present in membrane preparations from 335 samples (67%). In 260 of 500 samples (52%), two classes of [D-Trp6]-LH-RH membrane receptor sites were also detected, one class showing high affinity and low capacity, and the other class showing low affinity and high capacity; 178 biopsy samples (35.6%) exhibited binding sites for SS-14. Statistically significant inverse correlations were found between the binding capacities of estrogen and EGF receptors as well as between Bmax of progesterone and EGF receptors. Significant positive correlations were demonstrated between binding capacities of estrogen and progesterone and between Bmax of high affinity and low affinity binding sites of [D-Trp6]-LH-RH receptors. However, no correlation was found between the dissociation constants of different receptor sites in human breast cancer specimens. These results demonstrate that numerous human breast cancers, in addition to receptors for estrogen and progesterone, also show binding sites for EGF, [D-Trp6]-LH-RH and SS-14. The methods described herein permit a routine quantification of receptor sites for [D-Trp6]-LH-RH, SS-14, and EGF in membrane preparations of biopsy samples of breast cancer and can be used in conjunction with the determination of estrogen and progesterone receptors in nuclear-cytosolic extracts. The simultaneous measurements using a microanalytic approach allow the determination of peptide and steroid hormone receptors that might be involved in the response mechanisms of human breast cancer. It should be possible to correlate the levels of these receptors with clinical parameters to better identify endocrine-responsive neoplasms. This approach might be useful to guide a rational hormonal therapy in women with breast cancer.
采用多点分析法测定了500份乳腺癌标本中[D-色氨酸6]-促黄体生成素释放激素（[D-色氨酸6]-LH-RH）、生长抑素（SS-14）、表皮生长因子（EGF）以及雌激素和孕激素受体的结合能力和表观解离常数。在408例癌组织（81.6%）中发现雌激素的特异性结合位点大于10 fmol/mg胞浆蛋白，在340份标本（68%）中发现孕激素的特异性结合位点。335份样本（67%）的膜制剂中存在高亲和力的EGF受体。在500份样本中的260份（52%）中，还检测到两类[D-色氨酸6]-LH-RH膜受体位点，一类显示高亲和力和低容量，另一类显示低亲和力和高容量；178份活检样本（35.6%）表现出对SS-14的结合位点。在雌激素和EGF受体的结合能力之间以及孕激素的Bmax和EGF受体之间发现了具有统计学意义的负相关。在雌激素和孕激素的结合能力之间以及[D-色氨酸6]-LH-RH受体的高亲和力和低亲和力结合位点的Bmax之间发现了显著的正相关。然而，在人类乳腺癌标本中不同受体位点的解离常数之间未发现相关性。这些结果表明，除了雌激素和孕激素受体外，许多人类乳腺癌还显示出对EGF、[D-色氨酸6]-LH-RH和SS-14的结合位点。本文所述方法允许对乳腺癌活检样本膜制剂中[D-色氨酸6]-LH-RH、SS-14和EGF的受体位点进行常规定量，并且可与核-胞浆提取物中雌激素和孕激素受体的测定结合使用。使用微量分析方法进行同步测量可确定可能参与人类乳腺癌反应机制的肽和甾体激素受体。将这些受体的水平与临床参数相关联以更好地识别内分泌反应性肿瘤应该是可行的。这种方法可能有助于指导乳腺癌女性的合理激素治疗。
