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EDRI Federal Project Inventory:
70572-01 Estrogen/calcitriol in the Etiology of Breast Cancer
- Sponsor Organization: NIH/NCI
- Project Title: 70572-01 ESTROGEN/CALCITRIOL IN THE ETIOLOGY OF BREAST CANCER
- Project Focus: HUMAN HEALTH EFFECTS
- Description: In this project we plan to evaluate the interaction between estrogen
and the active vitamin D metabolite,1,25(OH)2D, in the etiology of
breast cancer, focussing on the role of insulin like growth factors
(IGFs) as mediators ofthis interaction with respect to tumor cell
proliferation. The hypothesis to be tested is that the
proproliferative action ofphysiologic concentrations of 1,25(OH)2D on
breast cancer development in the presence of estrogen is mediated
byIGFs and/or their receptors and binding proteins whose production is
controlled by 1,25(OH)2D and estrogen. The basisupon which this
hypothesis was formulated is that 1,25(OH)2D stimulates
proliferation of estrogen receptor positive(ER+) cell lines at low
concentrations when estrogen is present, but is antiproliferative at
these same concentrations inthe presence of an antiestrogen or
when added to estrogen receptor negative (ER-) breast cancer cells.
Since IGFs,their receptors, and binding proteins are produced by
breast cancer cells, regulate breast cancer cell growth, and vary
intheir response to estrogen in estrogen receptor positive and
negative cell lines, IGFs and their receptors/bindingproteins provide
an attractive mechanism by which the estrogen/1,25(OH)2D regulation of
breast cancer growth couldbe mediated. Three specific aims to test
this hypothesis are proposed: determine the mRNA and protein levels of
IGF-2, IGF-1 receptor (IGF-IR), and the IGF binding proteins (IGFBPs)
in MCF-7 (ER+) and MDA-MB-453 (ER-) cell linesin the presence of
17beta-estradiol (E2) and/or the antiestrogen ICl 164384; determine
the ability of 1,25(OH)2D atproproliferative (10[-11]M) and
antiproliferative (10[-8]M) concentrations to regulate estrogen and/or
antiestrogeninduced changes in IGF-2, IGF-1R, and IGFBP production in
the ER+ and ER- cell lines; and determine whether theinteraction
between 1,25(OH)2D and estrogen on the IGF system in vitro is
predictive of their role in regulating breastcancer growth in vivo.
- References:
- Category: MODELS
- Subcategory: BASIC RESEARCH
- Keywords for Experimental System/Species: IN VITRO, LABORATORY STUDY
- Keywords for Experimental Endpoints: GROWTH FACTORS, CARCINOGENESIS
- Chemical Agents: ESTRADIOL, ESTROGEN ANTIESTROGEN
- Performing Institution: NORTHERN CALIFORNIA INSTITUTE RES & EDUC
- Contact: CONTRACT PERSON: ELAINE C. LEE; BUILDING 31; 11A21; NATIONAL CANCER
INSTITUTE, NIH,BETHESDA, MD 20892-2590; 301-496-5515;
LEEE@OD.NCI.NIH.GOV
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