C-Jun N-terminal Kinase and Apoptosis in Breast Cancer.
Annual rept. 15 May 98-14 May 99
BAYLOR COLL OF MEDICINE HOUSTON TX
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Our previous studies show that c-Jun N-terminal kinase JNK participates in apoptosis signaling. JNK is differentially regulated by mitogenic and apoptotic stimuli in Jurkat T cells and in MCF-7 breast cancer cells, suggesting that duration of JNK activation may determine cell fate. A tetracycline-inducible system was used to control the expression of JNK1 and dominant-negative JNK1. This inducible system will be used to examine the duration hypothesis. In addition, we identified curcumin as an effective inhibitor for JNK activation by various stimuli. Curcumin may inhibit JNK activation by suppressing activation of JNK activators at the MAP3K level. The possibility to use curcumin to control the duration of JNK activation is currently under investigation. Tumor suppressor p53 is not required for radiation induced JNK activation. It is also not required for apoptosis induced by JNK activation. However, our data does not exclude that p53 may mediate JNK-induced apoptosis, which needs to be further studied. Both JNK activity and Fas expression can be induced by gamma radiation however, Fas expression is closely associated with a wild-type p53 status but not with the JNK activation. Our results show that induction of Fas expression is not the downstream effect for the JNK pathway.
- Anatomy and Physiology
- Medicine and Medical Research