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 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.
Ward
B K
BK
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Mark
P J
PJ
Ingram
D M
DM
Minchin
R F
RF
Ratajczak
T
T
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020104:Immunophilins / Q000096:biosynthesis* / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000378:metabolism; D022021:Tacrolimus Binding Proteins; D014407:Tumor Cells, Cultured / Q000502:physiology
D002352:Carrier Proteins; D000081406:Peptidyl-Prolyl Isomerase F; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D021983:Cyclophilins; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D019696:Peptidylprolyl Isomerase