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Tumorigenic role of tacrolimus through mTORC1/C2 activation in post-transplant renal cell carcinomas
by
Dankó, Titanilla
, Pápay, Judit
, Sebestyén, Anna
, Vetlényi, Enikő
, Végső, Gyula
, Sztankovics, Dániel
, Moldvai, Dorottya
, Patonai, Attila
, Piros, László
, Krencz, Ildikó
, Petővári, Gábor
, Hosszú, Ádám
, Márk, Ágnes
in
692/4028/67/589
/ 692/420/755
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Cell activation
/ Drug Resistance
/ End-stage renal disease
/ Epidemiology
/ Epithelial cells
/ Immunosuppression
/ Immunosuppressive agents
/ Intracellular signalling
/ Ischemia
/ Kidney cancer
/ Kidney diseases
/ Kidney transplantation
/ Kidneys
/ Molecular Medicine
/ Oncology
/ Rapamycin
/ Renal cell carcinoma
/ Signal transduction
/ Tacrolimus
/ TOR protein
/ Tumorigenesis
2024
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Tumorigenic role of tacrolimus through mTORC1/C2 activation in post-transplant renal cell carcinomas
by
Dankó, Titanilla
, Pápay, Judit
, Sebestyén, Anna
, Vetlényi, Enikő
, Végső, Gyula
, Sztankovics, Dániel
, Moldvai, Dorottya
, Patonai, Attila
, Piros, László
, Krencz, Ildikó
, Petővári, Gábor
, Hosszú, Ádám
, Márk, Ágnes
in
692/4028/67/589
/ 692/420/755
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Cell activation
/ Drug Resistance
/ End-stage renal disease
/ Epidemiology
/ Epithelial cells
/ Immunosuppression
/ Immunosuppressive agents
/ Intracellular signalling
/ Ischemia
/ Kidney cancer
/ Kidney diseases
/ Kidney transplantation
/ Kidneys
/ Molecular Medicine
/ Oncology
/ Rapamycin
/ Renal cell carcinoma
/ Signal transduction
/ Tacrolimus
/ TOR protein
/ Tumorigenesis
2024
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Tumorigenic role of tacrolimus through mTORC1/C2 activation in post-transplant renal cell carcinomas
by
Dankó, Titanilla
, Pápay, Judit
, Sebestyén, Anna
, Vetlényi, Enikő
, Végső, Gyula
, Sztankovics, Dániel
, Moldvai, Dorottya
, Patonai, Attila
, Piros, László
, Krencz, Ildikó
, Petővári, Gábor
, Hosszú, Ádám
, Márk, Ágnes
in
692/4028/67/589
/ 692/420/755
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Cell activation
/ Drug Resistance
/ End-stage renal disease
/ Epidemiology
/ Epithelial cells
/ Immunosuppression
/ Immunosuppressive agents
/ Intracellular signalling
/ Ischemia
/ Kidney cancer
/ Kidney diseases
/ Kidney transplantation
/ Kidneys
/ Molecular Medicine
/ Oncology
/ Rapamycin
/ Renal cell carcinoma
/ Signal transduction
/ Tacrolimus
/ TOR protein
/ Tumorigenesis
2024
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Tumorigenic role of tacrolimus through mTORC1/C2 activation in post-transplant renal cell carcinomas
Journal Article
Tumorigenic role of tacrolimus through mTORC1/C2 activation in post-transplant renal cell carcinomas
2024
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Overview
Background
Kidney transplant recipients (KTRs) face an increased risk of renal cell carcinoma (RCC), in which the immunosuppressive regimen plays an important role. This study aimed to identify intracellular signalling alterations associated with post-transplant (post-tx) tumour formation.
Methods
Expression of mTOR-related proteins were analysed in kidneys obtained from end-stage renal disease (ESRD) patients and RCCs developed in KTRs or non-transplant patients. The effects of tacrolimus (TAC) and rapamycin (RAPA) on mTOR activity, proliferation, and tumour growth were investigated through different in vitro and in vivo experiments.
Results
Elevated mTORC1/C2 activity was observed in post-tx RCCs and in kidneys of TAC-treated ESRD patients. In vitro experiments demonstrated that TAC increases mTOR activity in a normal tubular epithelial cell line and in the investigated RCC cell lines, moreover, promotes the proliferation of some RCC cell line. In vivo, TAC elevated mTORC1/C2 activity in ischaemic kidneys of mice and enhanced tumour growth in xenograft model.
Conclusions
We observed significantly increased mTOR activity in ischaemic kidneys and post-tx RCCs, which highlights involvement of mTOR pathway both in the healing or fibrotic processes of kidney and in tumorigenesis. TAC-treatment further augmented the already elevated mTOR activity of injured kidney, potentially contributing to tumorigenesis during immunosuppression.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
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