title: Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy.
abstract: The immunophilin FK506-binding protein 5 (FKBP51) is a scaffold protein that serves a pivotal role in the regulation of multiple signaling pathways, integrating external and internal stimuli into distinct signal outputs. In a previous study, we identified several genes that are significantly up- or downregulated in the peripheral white cells (PWCs) of colorectal adenocarcinoma (CRC) patients undergoing oxaliplatin-based chemotherapy. In our screening, FKBP51 gene expression was downregulated following chemotherapy. In order to determine whether this alteration in gene expression observed in PWCs may be detected at the protein level in tumors and metastases following the administration of adjuvant chemotherapy, an immunohistochemical analysis of FKBP51 in CRC and primary metastasis tissues was performed. The present study confirmed the downregulation of FKBP51 gene expression elicited by chemotherapy with folinic acid (leucovorin), fluorouracil and oxaliplatin in metastasized liver tissue that had been resected after the oxaliplatin-based chemotherapy, compared with tissue section samples of CRC from patients (prior to antineoplastic treatment). Furthermore, the results indicated that, in CRC tissue sections, the expression of FKBP51 protein is associated with an immature phenotype of stromal fibroblasts and with the epithelial-to-mesenchymal transition (EMT) phenotype, suggesting a role for this protein in the EMT process in CRC. Finally, the observation that only certain cells of the stroma express FKBP51 protein suggests a potential role for this immunophilin as a stroma cell subtype marker.
authors.affiliation: Developmental Biology Laboratory, UD- Biochemistry and Molecular Biology and Centre for Biomedical Research of the Canary Islands, La Laguna University, La Laguna, 38206 Tenerife, Spain; National Research Council, Institute of Endocrinology and Experimental Oncology, I-80131 Naples, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Rotoli
authors.affiliation: Service of Medical Oncology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain; Unit of Medical Oncology, Hospiten Hospitals, Santa Cruz de Tenerife, 38001 Tenerife, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Morales
authors.affiliation: Service of Pathology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Del Carmen Maeso
authors.affiliation: Laboratory of Biopathology, Hospiten Hospitals, 38010 Tenerife, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Del Pino García
authors.affiliation: Department of Physiology, Institute of Biomedical Technologies, School of Medicine and Centre for Biomedical Research of The Canary Islands, University of La Laguna, La Laguna, 38071 Santa Cruz de Tenerife, Spain.
authors.forename: Araceli
authors.initials: A
authors.lastname: Morales
authors.affiliation: Developmental Biology Laboratory, UD- Biochemistry and Molecular Biology and Centre for Biomedical Research of the Canary Islands, La Laguna University, La Laguna, 38206 Tenerife, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Ávila
authors.affiliation: Developmental Biology Laboratory, UD- Biochemistry and Molecular Biology and Centre for Biomedical Research of the Canary Islands, La Laguna University, La Laguna, 38206 Tenerife, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martín-Vasallo
keywords: FK506-binding protein 5; colorectal cancer; immunophilin; oxaliplatin