Inhibition of PI3K/AKT/mTOR and MAPK signaling pathways decreases progranulin expression in ovarian clear cell carcinoma (OCCC) cell line: a potential biomarker for therapy response to signaling pathway inhibitors

Journal Article · Wed Jan 15 04:00:00 EST 2020 · Medical Oncology (Online)

DOI:https://doi.org/10.1007/S12032-019-1326-5· OSTI ID:22938361

Perez-Juarez, Carlos Eduardo; Arechavaleta-Velasco, Fabian ^[1]; Zeferino-Toquero, Moises ^[2]; Alvarez-Arellano, Lourdes ^[3]; Estrada-Moscoso, Isaias ^[4]; Diaz-Cueto, Laura ^[1]

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1. Instituto Mexicano del Seguro Social, Unidad de Investigacion Medica en Medicina Reproductiva, UMAE Hospital de Gineco Obstetricia No. 4 “Luis Castelazo Ayala” (Mexico)
2. Instituto Mexicano del Seguro Social, Departamento de Cirugia Oncologica, Hospital de Gineco-Obstetricia No.3, Centro Medico Nacional La Raza (Mexico)
3. CONACYT-Hospital Infantil de Mexico Federico Gomez (Mexico)
4. UMAE Hospital de Gineco-Obstetricia No. 4 “Luis Castelazo Ayala”, IMSS, Departamento de Patologia (Mexico)

Patients with advanced stage ovarian clear cell carcinoma (OCCC) have a poor prognosis due to resistance to conventional platinum chemotherapy. Recent studies have demonstrated that PI3K/AKT/mTOR and ERK1/2 signaling pathways are involved in this chemoresistance. Progranulin (PGRN) overexpression contributes to cisplatin resistance of epithelial ovarian cancer cell lines. Also, PGRN expression is regulated by AKT/mTOR and ERK1/2 signaling pathways in different cell types. Thus, the present study was designed to identify if PGRN expression is regulated by AKT, mTOR, and ERK1/2 signaling pathways in the OCCC cell line TOV-21G. Cultured TOV-21G cells were incubated with different concentrations of pharmacological cell signaling inhibitors. PGRN expression and phosphorylation of ERK1/2, AKT, and mTOR were assessed by Western blotting. Inhibition of AKT, mTOR, and ERK1/2 significantly reduced PGRN expression. Cell viability was not affected, while cell proliferation significantly decreased with all inhibitors used in this study. These observations demonstrated that inhibition of PI3K/AKT/mTOR and ERK1/2 signaling pathways reduces PGRN expression in TOV-21G cells. Thus, PGRN could be considered as a candidate for explaining the high resistance to platinum-based treatment and a potential biomarker for therapy response to cell signaling inhibitors in patients with OCCC.

• OSTI ID: 22938361
• Journal Information: Medical Oncology (Online), Journal Name: Medical Oncology (Online) Journal Issue: 1 Vol. 37; ISSN 1559-131X
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BIOLOGICAL MARKERS
CARCINOMAS
CELL PROLIFERATION
CHEMOTHERAPY
OVARIES
PATIENTS
PHOSPHORYLATION