Prostate Cancer Cell Growth: Role of Neurotensin in Mediating Effect of Dietary Fat and Mechanism of Action
Abstract
The aims are (a) to determine the mechanism by which neurotensin (NT) enhances prostate cancer growth and (b) to test if NT released by eating contributes to cancer-promoting effects of high fat diets. Experiments show that NT transactivated the EGF receptor by liberating HB-ECF form the cell-surface by a metallo-protease-dependent and PKC-dependent mechanism. Activation of EGFR was followed by activation of MAp-kinase, P13-kinase, AKT and p70-S6-kinase, and in 24 hrs by a stimulation of DNA synthesis. We found that NT and EGF stimulated 3H-AA release form PC3 cells and that lipoxygenase (LOX) inhibitors blocked basal and NT-induced DNA synthesis. This suggests that EGF and NT act by way of PLA2 f-Lox and 12-LOX. Cell growth responses depend on the hormonal milieu. In the presence of a Gs stimulus, NT enhances cAMP production and his results in an inhibition of DNA synthesis. Thus, NT effects involve actions on protein kinase, LOX, EGFR, and cross-talk with adenylyl cyclases. Drug effects on NT-receptor function include calcium channel blockers, such as dihydropyridines, which indirectly block the first step in the signaling pathway, the formation of inositol phosphates. The mechanism is under study.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA419819
Entities
People
- Robert E. Carraway
Organizations
- University of Massachusetts