Differential expression of mTOR components in endometriosis and ovarian cancer: Effects of rapalogues and dual kinase inhibitors on mTORC1 and mTORC2 stoichiometry

Karly‐Rai Rogers‐Broadway, Karly-Rai Rogers-Broadway, Juhi Kumar, Cristina Sisu, Gurleen Wander, Emily Mazey, Jeyarooban Jeyaneethi, George Pados, Dimitrios Tsolakidis, Dimitris Tsolakidis, Eleftherios Klonos, Thomas W. Grunt, Thomas Grunt, Marcia Hall, Jayanta Chatterjee, Emmanouíl Karteris, Emmanouil Karteris
International journal of molecular medicine · 2018 · vol. 43(1) , pp. 47–56 · doi:10.3892/ijmm.2018.3967 · PMID:30387804 · PMC6257843 · W2897052907
article OA: gold CC0 ⤵ 15 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This study found increased mTOR expression in endometriosis and ovarian cancer, with DEPTOR upregulation following mTOR inhibition suggesting a tumor suppressor role, linking the mTOR pathway to both conditions.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

The study assessed expression of mTOR pathway components (mTOR, DEPTOR, Rictor, Raptor) in 24 patients with endometriosis and by qPCR/in silico comparisons in ovarian cancer, then tested how mTOR inhibitors (rapalogues including rapamycin/everolimus/deforolimus/temsirolimus, resveratrol, and the dual kinase inhibitor BEZ235) affected mTORC1/mTORC2-related signaling in the endometrioid ovarian carcinoma cell line MDAH-2774. The paper reports increased mTOR expression in endometriosis and ovarian endometrioid adenocarcinoma versus non-affected controls, downregulation of DEPTOR in advanced (III/IV) ovarian cancer stages, and that inhibitor treatment upregulated DEPTOR mRNA while rapamycin and BEZ235 decreased mTOR protein expression after 48 h without driving mTOR nuclear translocation. A key limitation is that drug effects were measured in a single in vitro cell line and the tissue comparisons for cancer included limited patient-context detail described in the text. This paper is centrally about endometriosis — it examines mTOR component expression in endometriosis and connects mTOR inhibition effects to an endometrioid ovarian cancer model.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Endometriosis is a well‑known risk factor for ovarian cancer. The genetic changes that characterise endometriosis are poorly understood; however, the mechanistic target of rapamycin (mTOR) pathway is involved. In this study, we investigated the expression of key mTOR components in endometriosis and the effects of rapalogues using an endometrioid ovarian carcinoma cell line (MDAH 2774) as an in vitro model. Gene expression of mTOR, DEPTOR, Rictor and Raptor was assessed by qPCR in 24 endometriosis patients and in silico in ovarian cancer patients. Furthermore, the effects of Rapamycin, Everolimus, Deforolimus, Temsirolimus, Resveratrol, and BEZ235 (Dactolisib, a dual kinase inhibitor) on mTOR signalling components was assessed. mTOR showed a significant increase in the expression in endometriosis and ovarian endometrioid adenocarcinoma patients compared to non‑affected controls. DEPTOR, an inhibitor of mTOR, was downregulated in the advanced stages of ovarian cancer (III and IV) compared to earlier stages (I and II). Treatment of MDAH‑2774 cells with the mTOR inhibitors resulted in the significant upregulation of DEPTOR mRNA, whereas treatment with rapamycin and BEZ‑235 (100 nM) resulted in downregulation of the mTOR protein expression after 48 h of treatment. None of the treatments resulted in translocation of mTOR from cytoplasm to nucleus. Upregulation of DEPTOR is a positive prognostic marker in ovarian cancer and is increased in response to mTOR pathway inhibition suggesting that it functions as a tumour suppressor gene in endometrioid ovarian carcinoma. Collectively, our data suggest the mTOR pathway as a potential connection between endometriosis and ovarian cancer and may be a potential target in the treatment of both conditions.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Endometriosis Mechanistic Target of Rapamycin Complex 1 Mechanistic Target of Rapamycin Complex 2 Ovarian Neoplasms Protein Kinase Inhibitors TOR Serine-Threonine Kinases Cell Line, Tumor Endometriosis Female Humans Mechanistic Target of Rapamycin Complex 1 Mechanistic Target of Rapamycin Complex 2 Ovarian Neoplasms Protein Kinase Inhibitors Signal Transduction TOR Serine-Threonine Kinases

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (46)

Cited by (15)

Source provenance

europepmc
last seen: 2026-06-11T06:19:48.454388+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:19:31.300640+00:00
License: CC0 · commercial use OK