2004
DOI: 10.1007/s00280-004-0843-9 View full text |Buy / Rent full text
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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, TGFbeta-RII, KRAS2, TP53, and CDKN2A. Cells were monitored for surv… Show more

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“…A specific phenotype has been reported in the BRCA2 heterozygous chicken B cell line DT40, characterized by reduced cell proliferation rates, increased cell death, greater sensitivity to DNA-damaging agents, and decreased RAD51 foci formation after irradiation. This phenotype is strikingly similar to the one described in the BRCA2 human ovarian tumor cell line TOV-81D, which retains both the normal and mutant copy of BRCA2 (13,14). Thus, it appears that, even in the context of cancer, the presence of a BRCA2 heterozygous mutation might be associated with distinct phenotypic changes.…”
Section: Introductionsupporting
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“…A specific phenotype has been reported in the BRCA2 heterozygous chicken B cell line DT40, characterized by reduced cell proliferation rates, increased cell death, greater sensitivity to DNA-damaging agents, and decreased RAD51 foci formation after irradiation. This phenotype is strikingly similar to the one described in the BRCA2 human ovarian tumor cell line TOV-81D, which retains both the normal and mutant copy of BRCA2 (13,14). Thus, it appears that, even in the context of cancer, the presence of a BRCA2 heterozygous mutation might be associated with distinct phenotypic changes.…”
Section: Introductionsupporting
“…An extensive description of the clinical data, BRCA1/2 mutation status, culture characteristics, and analyses associated with each sample is provided in Tables 1 and 2. The unique cell line used in this study, TOV-81D, has previously been established and described by our laboratory (13,14). All extractions were conducted within fewer than 6 months from resuscitation of frozen stocks established at the time of their original description.…”
Section: Cell Cultures and Clinical Materialsmentioning
“…S3). Similarly, it has been shown that the K-ras status in human ovarian cancer cell lines does not affect chemosensitivity to paclitaxel and cisplatin (17,18).…”
Section: Resultsmentioning
“…To test whether Brca1 status influences the sensitivity of OSE cells to drugs with different mechanisms of action, we compared the sensitivity of Brca1 wild-type and Brca1-deficient OSE cells to paclitaxel and cisplatin. OSE cell lines that are wild-type (C1, C2, C3, T1, T2, and T3) or deficient for Brca1 (BR2, BR5, BR6, TBR2, TBR5, and TBR6) were tested for their rate of survival in increasing concentrations of paclitaxel and cisplatin at doses that are effective in human ovarian cancer cell lines that harbor defined genetic alterations in genes such as Brca2, p53, K-ras, TGFb-RII, and CDNK2A (17). We showed that transformed Brca1 wild-type and Brca1-deficient mouse OSE cell lines have a similar sensitivity to the microtubule poison paclitaxel (Fig.…”
Section: Resultsmentioning
“…Studies using brca1-homozygous null murine ES cells have shown increased cell death induced by the alkylating agent, mitomycin C, platinum, and the topoisomerase inhibitors including doxorubicin (which is also an anthracycline) and mitoxantrone compared with wild-type cells (2 -4), but there were no differences for cells treated with antimetabolites. A study of a BRCA2 heterozygous mutant ovarian cancer cell line has shown heightened sensitivity to cisplatin compared with paclitaxel, but this study did not have a wild-type cell line control (5).…”
mentioning