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Abstract:
The enzyme, protein kinase C (PKC), is composed of a family of at least 11 isoforms which have distinct functions in signal transduction, tumor progression, and apoptosis. Elevated levels of PKC have been observed in breast cancers. The purpose of this project is to enhance radiation treatment through the use of isoform specific PKC inhibitors. Human breast tumor cell lines were treated with isoform specific AO (antisense oligonucleotides) and radiation. Cell survival and PKC isoform protein reduction were measured. Future experiments will address DNA damage following AO and radiation treatments as well compare the effectiveness of AO, chemical PKC inhibitors, and dominant negative PKCs in augmentation of radiation induced cell death. Results show that inhibition of PKC sigma and zeta by AO in combination with radiation treatment significantly reduces cell survival in two distinct breast tumor cell lines, while inhibition of PKC alpha, epsilon, or eta does not. Western blotting shows that AO are effective inhibitors of PKC isoforms, with PKC a and protein levels markedly reduced by AO treatment. These results support the use of isotype specific PKC inhibitors in combination with radiation treatment as a potential cancer therapy.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual summary rept. 1 Jul 99-30 Jun 00 |
| Pages: |
15 |
| Report Date: |
JUL 2000 |
| Contract Number: |
DAMD17-99-1-9449 |
| Report Number: |
A673583 |
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