Chemosensitivity and radiosensitivity profiles of four new human epithelial ovarian cancer cell lines exhibiting genetic alterations in BRCA2, TGFbeta-RII, KRAS2, TP53 and/or CDNK2A.
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, TGFbeta-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 gamma-irradiation. At the lowest doses, the TGFbeta-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 gamma-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 gamma-irradiation. In contrast, sensitivity to camptothecin or paclitaxel was not significantly different between all cell lines, irrespective of the mutation status of BRCA1, BRCA2, TGFbeta-RII, KRAS2, TP53, and CDKN2A. The observed responses to treatment are consistent with the current knowledge concerning BRCA2, TGFbeta-RII, KRAS2, TP53, and/or CDKN2A aberrant function.
Samouëlian
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V
Centre de recherche CHUM/Institut du cancer de Montréal, Hôpital Notre Dame, 1560, rue Sherbrooke est, H2L 4M1, Montreal, QC, Canada H2L 4M1.
Maugard
C M
CM
Jolicoeur
M
M
Bertrand
R
R
Arcand
S L
SL
Tonin
P N
PN
Provencher
D M
DM
Mes-Masson
A-M
AM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D024522:Genes, BRCA2; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011836:Radiation Tolerance; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D014407:Tumor Cells, Cultured; D018631:ras Proteins
D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins