Chemosensitivity and radiosensitivity profiles of four new human epithelial ovarian cancer cell lines exhibiting genetic alterations in BRCA2, TGFβ-RII, KRAS2, TP53 and/or CDNK2A
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To address the cellular basis for the response to ovarian cancer treatment, we characterized the chemosensitivity and radiosensitivity of four human epithelial ovarian cancer cell lines that harbor different genetic alterations. The TOV-21G, TOV-81D, OV-90, and TOV-112D cell lines were derived from ovarian tumors (TOV) or ascites (OV) from chemotherapy- and radiotherapy-naive patients and were characterized by their mutation spectrum of BRCA2, TGFβ-RII, KRAS2, TP53, and CDKN2A. Cells were monitored for survival following exposure at various concentrations to different cytotoxic agents including cisplatin, camptothecin or paclitaxel or to different doses of γ-irradiation. At the lowest doses, the TGFβ-RII-mutated and KRAS2-mutated cell line, TOV-21G, and the BRCA2-mutated cell line, TOV-81D, demonstrated a significantly higher sensitivity to cisplatin and γ-irradiation than the TP53-mutated cell lines, TOV-112D and OV-90. At higher doses, differences between the TP53-mutated lines were observed with TOV-112D being less sensitive to cisplatin than OV-90 that also harbors a CDNK2A mutation. All cell lines were similarly sensitive to high doses of γ-irradiation. In contrast, sensitivity to camptothecin or paclitaxel was not significantly different between all cell lines, irrespective of the mutation status of BRCA1, BRCA2, TGFβ-RII, KRAS2, TP53, and CDKN2A. The observed responses to treatment are consistent with the current knowledge concerning BRCA2, TGFβ-RII, KRAS2, TP53, and/or CDKN2A aberrant function.
KeywordsChemosensitivity Radiosensitivity Ovarian epithelial cell line Genetic alterations in BRCA2, TGFβ-RII, KRAS2, TP53, and/or CDNK2A
We are grateful to Louise Champoux for her technical assistance. This work was supported by a grant from the Montreal Breast Cancer Foundation and the Fondation Jocelyn Gauvin. V.S. was supported by la CAMPLP (Caisse d’Assurance-Maladie des Professions Libérales de Province) and C.M.M by a fellowship from the Fondation pour la Recherche Médicale and a Bourse d’excellence from the Ministère de l’Education du Québec. P.N.T. is a recipient of a Frazer, Monat, and McPherson Scholarship and the Stewart Fellowship in Research/Clinical Hematology and Oncology. R.B. is a recipient of a Chercheur Senior, D.M.P. is a recipient of a Chercheur-Clinicien Senior, and A.-M.M.-M. is a recipient of a Chercheur National, all fellowships provided by the Fonds de Recherche en Santé du Québec.
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