BCL-2 family protein expression and platinum drug resistance in ovarian carcinoma

The expression of the BCL-2 family proteins, BCL-2, BAX, BCL XL and BAK have been determined in a panel of 12 human ovarian carcinoma cell lines encompassing a wide range in sensitivity to cisplatin. Whereas BAX, BCL XL and BAK levels did not correlate with sensitivity, there was a statistically sig...

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Bibliographic Details
Published in:British journal of cancer Vol. 82; no. 2; pp. 436 - 440
Main Authors: Beale, P J, Rogers, P, Boxall, F, Sharp, S Y, Kelland, L R
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.01.2000
Nature Publishing Group
Subjects:
Antineoplastic agents
Antineoplastic Agents - pharmacology
Apoptosis
Base Sequence
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer Research
Chemotherapy
Cisplatin - pharmacology
DNA Damage
Drug Resistance
Drug Resistance, Neoplasm
Epidemiology
Female
Genes, bcl-2 - genetics
Humans
Medical research
Medical sciences
Molecular Medicine
Molecular Sequence Data
Oncology
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
Pharmacology. Drug treatments
Protein expression
Proteins
Regular
regular-article
Transplantation, Heterologous
Tumor Cells, Cultured
United Kingdom > UK
United States > US
ovarian carcinoma
BCL-2
platinum
resistance
Antineoplastic agent
Human
Animal model
Carcinoma
Rodentia
Malignant tumor
Gene expression
Cisplatin
Female genital diseases
Ovarian diseases
Ovary
Vertebrata
Chemotherapy
Mammalia
Treatment
Mouse
Animal
C-Onc gene
Established cell line
Genetics
Negative therapeutic reaction
Protooncogene
Platinum II Complexes
ISSN:0007-0920, 1532-1827
Online Access:Get full text
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Summary:The expression of the BCL-2 family proteins, BCL-2, BAX, BCL XL and BAK have been determined in a panel of 12 human ovarian carcinoma cell lines encompassing a wide range in sensitivity to cisplatin. Whereas BAX, BCL XL and BAK levels did not correlate with sensitivity, there was a statistically significant inverse correlation ( r = –0.81; P = 0.002) between growth inhibition by cisplatin and BCL-2 levels. In sublines possessing acquired resistance to various platinum-based drugs or across a panel of human ovarian carcinoma xenografts, there was no consistent pattern of BCL-2 expression. Two relatively sensitive lines (A2780 and CH1) have been stably transfected with bcl-2 and bcl XL respectively and two relatively resistant lines (A2780cisR and SKOV-3) stably transfected with bax. Overexpression of BCL-2 in A2780 cells led to resistance to cisplatin compared to the vector control when assayed at 48 h post-drug incubation but a significant increase in sensitivity at 96 h. Relative rates of apoptosis at 48- and 96-h post-cisplatin exposure mirrored the growth inhibition. There was no significant difference in sensitivity of the pair of lines by clonogenic assay. No significant changes in chemosensitivity to a variety of DNA-damaging or tubulin-interactive agents were observed in the remaining transfected lines. Taken together, these results suggest that, in human ovarian carcinoma cells, high BCL-2 levels (either naturally occurring or through gene transfection) confers a trend towards sensitivity not resistance to platinum drugs. © 2000 Cancer Research Campaign
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ISSN:0007-0920
1532-1827
DOI:10.1054/bjoc.1999.0939