Abstract
We analyzed clonal populations of ovarian cancer cells for heterogeneity in p53 mutations (exons 4-9) and chemosensitivity. UL-3A cells were developed from a patient with stage IIIC ovarian adenocarcinoma. Heterogeneity in p53 mutations was demonstrated, ranging from point mutations to deletions in exons 4, 6 and 7. UL-3A cells contained two point mutations, in codon 248 of exon 7 and in codon 76 of exon 4. Five groups of clones were identified according to the p53 mutations. UL-3A clones with low p53 levels were more sensitive to CDDP (LD50 <8.0 microg/ml). Heterogeneity of p53 mutations may provide growth advantage during disease progression or chemotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Cisplatin / pharmacology
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Clone Cells
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DNA Mutational Analysis
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DNA, Neoplasm / chemistry
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DNA, Neoplasm / genetics
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Female
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Genetic Heterogeneity
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Humans
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Immunoblotting
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Lethal Dose 50
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Mutation
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / pathology*
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Paclitaxel / pharmacology
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Polymorphism, Single-Stranded Conformational
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Topotecan / pharmacology
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
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Tumor Suppressor Protein p53 / genetics*
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Tumor Suppressor Protein p53 / metabolism
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bcl-2-Associated X Protein
Substances
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Antineoplastic Agents
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DNA, Neoplasm
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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Topotecan
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Paclitaxel
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Cisplatin