Role of Lysophospholipids in the Initiation, Progression and Therapy of Breast Cancer
Abstract
Since the initiation of this proposal, we have demonstrated that while LPP1 and LPP3 mRNAlevels are decreased approximately 2 fold in breast cancer cells, autotaxin levels areincreased approximately 28 fold in breast cancer cells isolated directly from patients.This should result in increased LPA and S1P production by breast cancer cells in patients.Using a novel enzyme activity assay, we have demonstrated that autotaxin acitivity is notsignificantly different in blood from control and breast cancer patients. Thus, theincreased mRNA levels in tumor cells are not translated into increased autotaxin activityin the blood stream.We have demonstrated that downregulation of autotaxin by RNAi results in a decreasedsignaling, a novel S phase arrest and apoptosis in breast cancer cells.We have utilized a novel Si1P antibody to neutralize S1P in vitro and are currentlytreating mice with breast cancer xenografts to determine effects on cell growth.We have established transgenic mice expression the three LPA receptors as well asautotaxin in breast epithelium. We have obtained a LPP transgenic mouse to determine theeffects of degradation of LPA and S1P on breast function and tumorigenesis by crossing tothe above mice and to tumor prone mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2005
- Accession Number
- ADA452247
Entities
People
- Makiko Goto
- Shuying Liu
Organizations
- The University of Texas MD Anderson Cancer Center