Expression of FK506 binding protein 65 (FKBP65) is decreased in epithelial ovarian cancer cells compared to benign tumor cells and to ovarian epithelium

Abstract

FK506 binding protein 65 (FKBP65) belongs to a group of proteins termed immunophilins that have a high binding affinity to immunosuppressant drugs as FK506 (tacrolimus) and rapamycin (sirolimus). Treatment of female premenopausal women with tacrolimus, which binds to FKBP65, has been reported to be followed by a strongly increased risk of ovarian cysts. We performed the present study to reveal how FKBP65 is expressed in the ovary and in ovarian tumors and to see if this expression might be related to ovarian tumor development, a relationship we have found in colorectal cancer. Biopsies from prospectively collected samples from ovaries and benign, borderline, and invasive ovarian tumors were analyzed for expression of FKBP65 by immunohistochemistry. The expression was compared to survival and several clinicopathological parameters. FKBP65 is strongly expressed in ovarian epithelium and in benign ovarian tumor cells. In the ovary, a positive staining was also found in endothelial cells of blood vessels. In non-invasive and in invasive malignant tumor cells, a decreased staining was observed, which was not correlated to stage, histology, or survival. A significant inversed correlation to expression of p53 was found. The differential expression of FKBP65 indicates a role in ovarian physiology as well as in ovarian tumor development. Our observations and the chromosomal localization of the FKBP65 gene indicate a tumor suppressor function of the FKBP65 protein in ovarian carcinogenesis.

FK506 Binding Protein 10 Is Overexpressed and Promotes Renal Cell Carcinoma

“…in ovarian tumor [22,23] . Thus, whether FKBP10 serves as tumor suppressor or oncogene depends on the different tissues.…”

“…Different from all the other family proteins, FKBP10 contains 4 PPIase domains [20,21] . FKBP10 has been implicated in ovarian cancer [17,22] , colorectal cancer [23] , KRAS-induced lung cancer [18] , prostate cancer [24], and leukemia [25] .…”

Gene Set Analysis of Survival Following Ovarian Cancer Implicates Macrolide Binding and Intracellular Signaling Genes

“…This gene set originated from the GO molecular classification which indicates that the gene set is a “child” of the drug binding gene set and a “parent” to the FK506 binding gene set which contains genes that interact “selectively and non-covalently with the immunosuppressant FK506”(36). Henriksen et al (37) found that the FK506 binding protein 65 (FKBP65) was highly expressed in ovarian epithelium and in benign ovarian tumor cells, while the expression levels were lower in invasive tumor cells. FKBP65 was also found to be inversely associated with expression of p53 (37).…”

“…Henriksen et al (37) found that the FK506 binding protein 65 (FKBP65) was highly expressed in ovarian epithelium and in benign ovarian tumor cells, while the expression levels were lower in invasive tumor cells. FKBP65 was also found to be inversely associated with expression of p53 (37). …”

The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

“…This suggests that FKBP65 may be involved in colorectal carcinogenesis and could be a novel colorectal biomarker 183 . FKBP65 is strongly expressed in normal and benign ovarian epithelium but a low expression in high grade serous carcinoma (HGSC) is probably due to frequent loss of chromosome 17 in HGSC 185,186 . This indicates a tumour suppressor function for FKBP65 in ovarian carcinomas.…”