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.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW000927-02
Application #
2883765
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Michels, Kathleen M
Project Start
1998-03-01
Project End
2001-02-28
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Pharmacology
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461