Chemosensitivity and radiosensitivity profiles of four new human epithelial ovarian cancer cell lines exhibiting genetic alterations in BRCA2, TGFß-RI

V. Samouëlian1, 2, C. M. Maugard1, 3, M. Jolicoeur4, R. Bertrand1, 3, S. L. Arcand5, P. N. Tonin5, 6, D. M. Provencher1, 7 and A.-M. Mes-Masson1, 3

(1) Centre de recherche CHUM/Institut du cancer de Montréal, Hôpital Notre Dame, 1560, rue Sherbrooke est, Montreal, QC, Canada, H2L 4M1
(2) Present address: Clinique de gynécologie-obstétrique, Unité de recherche clinique, Hôpital Jeanne de Flandre, CHRU, Lille, France
(3) Département de Médecine, Université de Montréal, Succursale Centre-ville, C.P. 6128, Montreal, QC, Canada, H3C 3J7
(4) Département de Radiologie, Radio-oncologie et Médecine nucléaire, Université de Montréal, Succursale Centre-ville, C.P. 6128, Montreal, QC, Canada, H3C 3J7
(5) The Research Institute of the McGill University Health Centre, Medical Genetics, Montreal General Hospital, Room L10-120, 1650 Cedar Avenue, Montreal, QC, Canada, H3G 1A4
(6) Departments of Medicine and Human Genetics, Stewart Biology Building, N5/13, McGill University, 1205 Docteur Penfield, Montreal, QC, Canada, H3A 1B1
(7) Division of Gynecologic Oncology, Department of Obstetric-Gynecology, Université de Montréal, Succursale Centre-ville, C.P. 6128, Montreal, QC, Canada, H3C 3J7

Received: 1 February 2004 Accepted: 9 April 2004 Published online: 16 July 2004

Abstract 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, TGF-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 -irradiation. At the lowest doses, the TGF-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 -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 -irradiation. In contrast, sensitivity to camptothecin or paclitaxel was not significantly different between all cell lines, irrespective of the mutation status of BRCA1, BRCA2, TGF-RII, KRAS2, TP53, and CDKN2A. The observed responses to treatment are consistent with the current knowledge concerning BRCA2, TGF-RII, KRAS2, TP53, and/or CDKN2A aberrant function.
Keywords Chemosensitivity - Radiosensitivity - Ovarian epithelial cell line - Genetic alterations in BRCA2, TGF-RII, KRAS2, TP53,