Expression of the estrogen receptor-associated immunophilins, cyclophilin 40 and FKBP52, in breast cancer

The estrogen receptor alpha (ER alpha) is implicated in the development of breast cancer. The immunophilins, cyclophilin 40 (CyP40) and FKBP52, are as sociated with ER alpha and other steroid receptors in mutually exclusive he terocomplexes and may differentially modulate receptor activity. Since prev ious studies have not assessed the levels of these immunophilins in breast cancer, we examined 10 breast cancer cell lines for mRNA and protein expres sion of CyP40 and FKBP52 and for amplification of the CyP40 gene. In additi on, 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 si gnificant 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 signifi cantly higher in ER alpha-positive compared with ER alpha-negative cell lin es. However, CyP40 mRNA expression did not correlate with protein expressio n, nor did expression of this immunophilin correlate with ER alpha status. Relatively high expression of CyP40 in one cell line (BT-20) could be attri buted to amplification of the CyP40 gene. Both immunophilins were also ubiq uitously expressed in breast carcinomas, and we demonstrate for the first t ime that both CyP40 and FKBP52 mRNA are overexpressed in breast tumors comp ared to matched normal breast controls. The overexpression of CyP40 and FKB P52, coupled with relative differences in their expression in tumors, may h ave important functional implications for ER alpha and other steroid recept ors in breast cancer.