| Title: |
BCL-2 family protein expression and platinum drug resistance in ovarian carcinoma. |
| Authors: |
Beale, PJ; Rogers, P; Boxall, F; Sharp, SY; Kelland, LR |
| Source: |
440 ; 436 |
| Publisher Information: |
Springer Nature [academic journals on nature.com] |
| Publication Year: |
1999 |
| Collection: |
Imperial College London: Spiral |
| Subject Terms: |
Antineoplastic Agents; Apoptosis; Base Sequence; Cisplatin; DNA Damage; Drug Resistance; Neoplasm; Female; Genes; bcl-2; Humans; Molecular Sequence Data; Ovarian Neoplasms; Transplantation; Heterologous; Tumor Cells; Cultured |
| Subject Geographic: |
England |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
British Journal of Cancer; http://hdl.handle.net/10044/1/92189 |
| DOI: |
10.1054/bjoc.1999.0939 |
| Availability: |
http://hdl.handle.net/10044/1/92189; https://doi.org/10.1054/bjoc.1999.0939 |
| Rights: |
© 2000 Cancer Research Campaign. This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication References ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.E4EB417 |
| Database: |
BASE |