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 mRNA levels are decreased approximately 2 fold in breast cancer cells, autotaxin levels are increased 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 activity is not significantly different in blood from control and breast cancer patients. Thus, the increased mRNA levels in tumor cells are not translated into increased autotaxin activity in the blood stream. We have demonstrated that down regulation of autotaxin by RNAi results in a decreased signaling, 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 currently treating mice with breast cancer xenografts to determine effects on cell growth. We have established transgenic mice expression the three LPA receptors as well as autotaxin in breast epithelium. We have obtained a LPP transgenic mouse to determine the effects of degradation of LPA and S1P on breast function and tumorigenesis by crossing to the above mice and to tumor prone mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA452618
Entities
People
- Makiko Umezu-goto
- Shuying Liu
Organizations
- The University of Texas MD Anderson Cancer Center