Taxol is a natural product which has significant antitumor activity in a large number of human tumors. It has recently become appreciated that in addition to stabilizing microtubules and blocking cell cycle progress, taxol can alter gene expression by interacting with the MAP-kinase signal transduction pathway. Previous studies from the foreign and US PIs had demonstrated that tyrosine phosphorylation of the adaptor protein, Shc, and formation of Shc/grb2/SOS complexes occurs in a taxol-treated murine macrophage cell line. The investigators propose to extend these observations to examine human ovarian carcinoma cells.
The specific aims are to: 1. Study the effect of taxol on activation of the MAP-kinase pathway in human ovarian carcinoma cell lines; 2. Study the effect of taxotere and other taxol analogs compared to that of taxol on the activation of the Ras/MAPK signaling pathway and the relationship of this activity to effects on microtubule stabilization and cytotoxicity; 3. Compare taxol and taxotere in MAPK signaling pathway in taxol-sensitive and taxol-resistant human ovarian carcinoma cells.
| Ofir, R; Seidman, R; Rabinski, T et al. (2002) Taxol-induced apoptosis in human SKOV3 ovarian and MCF7 breast carcinoma cells is caspase-3 and caspase-9 independent. Cell Death Differ 9:636-42 |
| Seidman, R; Gitelman, I; Sagi, O et al. (2001) The role of ERK 1/2 and p38 MAP-kinase pathways in taxol-induced apoptosis in human ovarian carcinoma cells. Exp Cell Res 268:84-92 |
