PhD Scientific Days 2018

Oral presentations: Oncology

mTORC2 as a potential therapeutic target in renal cell carcinoma of kidney transplant recipients

Előadó neve

Dr. Krencz, Ildikó

Előadó munkahelye

1st Department of Pathology and Experimental Cancer Research, Semmelweis University

Előadó telefonszáma

+36203764491

Előadó e-mail címe

krencz.ildiko@gmail.com

Az előadás címe

mTORC2 as a potential therapeutic target in renal cell carcinoma of kidney transplant recipients

Szerző(k) neve és munkahelye

Ildikó Krencz1, Gyula Végső2, Anna Sebestyén1, Titanilla Dankó1, Gábor Petővári1, Zoltán Hujber1, Judit Pápay1

1 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2 Department of Transplantation and Surgery, Semmelweis University, Budapest

Bemutatás módja

Poszter

Szekció

Oral presentations: Oncology

Language of the presentation

Hungarian

Témacsoport

oncology (experimental and clinical)

Összefoglaló szövege

Introduction: The PI3K/Akt/mTOR pathway has a fundamental role in renal physiology and its inhibitors are used as immunosuppressive as well as anti-tumour agents. Recent studies suggest that immunosuppressive treatment may influence mTOR pathway activation.
Aims: The aim of our study was to analyse the role of mTORC1/C2 activity in post-transplant renal cell carcinoma (RCC).
Method: Protein expression of p-mTOR (catalytic subunit of mTORC1 and mTORC2), p-S6 (mTORC1-related protein) and Rictor (mTORC2-related protein) was assessed by immunohistochemistry in post-transplant (n=46) and non-transplant (n=46) RCCs. Tissues from patients with end-stage renal disease (ESRD) (n=10) and normal kidney (n=3) were also studied. RCC (786-O, A498) and normal proximal tubular cell lines (HK-2, NRK) were treated with tacrolimus (calcineurin inhibitor), rapamycin (mTORC1 inhibitor), and PP242 (mTORC1/C2 inhibitor) and Alamar Blue proliferation assay was performed.
Results: Expression of p-S6 and p-mTOR was weak and expression of Rictor was high in normal tubular epithelial cells. In ESRD, expression of p-mTOR, p-S6, and Rictor appeared to be higher in transplant recipients compared to those who have not received immunosuppression. Expression of p-mTOR and Rictor was significantly higher in RCCs of diseased native kidneys of renal transplant recipients compared to RCCs developed in healthy individuals (P<0.01). Rapamycin inhibited the proliferation of NRK, HK-2 and 786-O cells (P<0.05), however, A498 was rapamycin-resistant. PP242 suppressed proliferation more effectively in all cell lines (P<0.001). Tacrolimus did not affect proliferation at immunosuppressive dose, however, higher concentration promoted proliferation of A498 cells (P<0.05).
Conclusion: There are few evidences for the protective role of mTOR inhibitors as immunosuppressive agents against post-transplant renal malignancies. Our results highlighted the role of mTORC2 in the pathobiology of post-transplant RCCs. Based on our results, using dual mTORC1/C2 inhibitors as immunosuppressive and/or anti-tumour treatment may represent a promising opportunity to prevent and cure post-transplant RCCs.

Data of the presenter

Supported by the ÚNKP-17-3 New National Excellence Program of the Ministry of Human Capacities, scientific grant of the Hungarian Respiratory Foundation, Bolyai Found of Hungarian Academy Sciences, and Semmelweis University Innovation Found STIA-KF-17.

Doctoral School: Doctoral School of Pathological Sciences
Program: Oncology
Supervisor: Judit Pápay
E-mail address: krencz.ildiko@gmail.com

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1307

Authors (legacy)

Ildikó Krencz1, Gyula Végső2, Anna Sebestyén1, Titanilla Dankó1, Gábor Petővári1, Zoltán Hujber1, Judit Pápay1

1 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2 Department of Transplantation and Surgery, Semmelweis University, Budapest