Estrogen-Modulated Response of Breast Cancer To Vitamin D and Its Analogs: Role of IGF
Abstract
The principal goal of the proposed studies is to determine if 1,25-dihydroxy-vitamin D3 and some of its analogues inhibit proliferation of human breast cancer cells by altering the expression and function of endothelial differentiation gene-encoded G protein-coupled receptors (Edg Rs) for lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). Estrogen receptor positive and estrogen receptor negative cells express predominantly Edg-2 and Edg-4 Rs for LPA and Edg-3 for Sip, which transduce proliferative responses by direct nuclear signaling, through MAP kinase, and stimulate secretion of type II insulin-like growth factor (IGF-II). The proliferation of breast cancer cells induced by LPA and S1P is inhibited significantly by 10-10-10-8 M 1,25- dihydroxy-vitamin D3 analogue. We aim to delineate the effects of 1,25-dihydroxy- vitamin D3 analogues on Edg R expression and biochemical signaling, IGF-II receptor expression and secretion of IGF-II. Results are expected to further our understanding of abnormal growth regulatory mechanisms in breast cancer and may lead to Edg R directed modalities of treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA380441
Entities
People
- Edward J. Goetzl
- Hana Dolezalova
Organizations
- University of California, San Francisco