Journal
MEDICAL ONCOLOGY
Volume 37, Issue 1, Pages -Publisher
HUMANA PRESS INC
DOI: 10.1007/s12032-019-1326-5
Keywords
Progranulin; Ovarian clear cell carcinoma; Signal transduction pathways; Pharmacological inhibitors; Biomarker
Categories
Funding
- Fondo de Investigacion en Salud, Instituto Mexicano del Seguro Social [FIS/IMSS/PROT/G15/1464, FIS/IMSS/PROT/G11/987]
- CONACYT, Mexico [365460/245530]
- Instituto Mexicano del Seguro Social, Ciudad de Mexico, Mexico [Matricula: 99095927]
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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.
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