Ward B K, Mark P J, Ingram D M, Minchin R F, Ratajczak T
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Breast Cancer Res Treat. 1999 Dec;58(3):267-80. doi: 10.1023/a:1006390804515.
The estrogen receptor alpha (ER alpha) is implicated in the development of breast cancer. The immunophilins, cyclophilin 40 (CyP40) and FKBP52, are associated with ER alpha and other steroid receptors in mutually exclusive heterocomplexes and may differentially modulate receptor activity. Since previous studies have not assessed the levels of these immunophilins in breast cancer, we examined 10 breast cancer cell lines for mRNA and protein expression of CyP40 and FKBP52 and for amplification of the CyP40 gene. In addition, 26 breast carcinomas, including seven with matched normal breast tissue, were examined for mRNA expression of both immunophilins. CyP40 and FKBP52 were ubiquitously expressed in breast cancer cell lines, but there were significant differences in their pattern of expression. FKBP52 protein levels were generally an order of magnitude greater than those for CyP40. FKBP52 mRNA expression correlated strongly with protein expression and was significantly higher in ER alpha-positive compared with ER alpha-negative cell lines. However, CyP40 mRNA expression did not correlate with protein expression, nor did expression of this immunophilin correlate with ER alpha status. Relatively high expression of CyP40 in one cell line (BT-20) could be attributed to amplification of the CyP40 gene. Both immunophilins were also ubiquitously expressed in breast carcinomas, and we demonstrate for the first time that both CyP40 and FKBP52 mRNA are overexpressed in breast tumors compared to matched normal breast controls. The overexpression of CyP40 and FKBP52, coupled with relative differences in their expression in tumors, may have important functional implications for ER alpha and other steroid receptors in breast cancer.
雌激素受体α（ERα）与乳腺癌的发生发展有关。亲免素，即亲环素40（CyP40）和FK506结合蛋白52（FKBP52），在互斥的异源复合物中与ERα及其他类固醇受体相关联，可能会对受体活性产生不同的调节作用。由于先前的研究尚未评估这些亲免素在乳腺癌中的水平，我们检测了10种乳腺癌细胞系中CyP40和FKBP52的mRNA及蛋白表达情况，以及CyP40基因的扩增情况。此外，我们还检测了26例乳腺癌组织（其中7例有配对的正常乳腺组织）中这两种亲免素的mRNA表达。CyP40和FKBP52在乳腺癌细胞系中普遍表达，但它们的表达模式存在显著差异。FKBP52的蛋白水平通常比CyP40高一个数量级。FKBP52的mRNA表达与蛋白表达密切相关，并且在ERα阳性细胞系中显著高于ERα阴性细胞系。然而，CyP40的mRNA表达与蛋白表达不相关，该亲免素的表达也与ERα状态无关。在一种细胞系（BT - 20）中CyP40的相对高表达可能归因于CyP40基因的扩增。这两种亲免素在乳腺癌组织中也普遍表达，并且我们首次证明，与配对的正常乳腺对照相比，CyP40和FKBP52的mRNA在乳腺肿瘤中均有过表达。CyP40和FKBP52的过表达，以及它们在肿瘤中表达的相对差异，可能对乳腺癌中的ERα及其他类固醇受体具有重要的功能意义。
