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2015 ; 10
(6
): 2224-2230
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Downregulation of telomerase maintenance-related ACD expression in patients
undergoing immunosuppresive therapy following kidney transplantation
#MMPMID26668621
Witkowska A
; Strzalka-Mrozik B
; Owczarek A
; Gola J
; Mazurek U
; Grzeszczak W
; Gumprecht J
Exp Ther Med
2015[Dec]; 10
(6
): 2224-2230
PMID26668621
show ga
Chronic administration of immunosuppressants has been associated with long-term
consequences, including a higher risk of neoplasm development. The processes
regulating telomere function exert a major influence on human cancer biology. The
present study aimed to assess the effect of immunosuppressive therapy on the
expression of genes associated with telomere maintenance and protection in
patients following renal transplantation. A total of 51 patients that had
undergone kidney transplantation and 54 healthy controls were enrolled in the
study. The 51 transplant patients received a three-drug immunosuppressive regimen
consisting of cyclosporine A, prednisone and mycophenolate mofetil. In stage 1 of
the study, the expression profiles of 123 transcripts, which represented 70
genes, were assessed in peripheral mononuclear blood cells using an
oligonucleotide microarray technique in 8 transplant recipients and 4 healthy
control subjects. Among the analyzed transcripts, the expression levels of 4
differed significantly between the studied groups; however, only the ACD
(adrenocortical dysplasia homolog) gene, encoding the telomere-binding protein
POT1-interacting protein 1 (TPP1), was sufficiently specific for telomere
homeostasis. The expression of ACD was downregulated in transplant recipients
(fold change, 2.11; P=0.006). In stage 2 of the study, reverse
transcription-quantitative polymerase chain reaction analysis of ACD, DKC1 and
hTERT mRNA was conducted for all transplant patients and control subjects. The
results confirmed the downregulation of the ACD gene in patients that had
received immunosuppressive therapy (P=0.002). The results of the present study
indicate that the downregulation of ACD gene transcription, and thus TPP1 protein
expression, may enhance the capacity for cell immortalization, despite normal
levels of other key telomere maintenance factors, in patients undergoing
immunosuppressive therapy. Furthermore, the results indicate that TPP1 has
potential for use as an early clinical marker and/or therapeutic target for
cancer in patients following organ transplantation.