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Abstract:
TRAIL induces apoptosis in five of six prostate cancer cell lines. The cell line LNCaP is resistant to TRAIL treatment. Highly constitutive expression of AKT was found in LNCaP cells, and suppression of AKT activity by the PI-3 kinase inhibitors wortmanin and Ly 294002 renders LNCaP cells sensitive to TRAIL. Infection of LNCaP cells with a constitutively active AKT reverses the wortmanin effect. Thus, elevated AKT protects LNCaP cells from TRAIL-induced apoptosis. Bcl-2 dimerization varies in six different prostate cell lines. Overexpression of bcl-2 in LNCaP cells inhibits cytochrome c release from mitochondria when TRAIL is used in combination with wortmanin, suggesting that the mitochondria mediated apoptosis pathway is crucial. The role of mitochondrial superoxide production in TRAIL-induced apoptosis is currently being studied in smooth muscle cells deficient in each superoxide dismutase.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual summary rept. 1 Jul 2000-30 Jun 2001 |
| Pages: |
18 |
| Report Date: |
JUL 2001 |
| Contract Number: |
DAMD17-99-1-9516 |
| Report Number: |
A326693 |
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