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EDRI Federal Project Inventory:
61668-02 Genistein and Cancer Prevention–Mechanisms and Models
- Sponsor Organization: NIH/NCI
- Project Title: 61668-02 GENISTEIN AND CANCER PREVENTION--MECHANISMS AND MODELS
- Project Focus: HUMAN HEALTH EFFECTS
- Description: This proposal is one of three projects forming an Interactive ROI
application entitled "Anti-cancer mechanisms of thesoy isoflavone
genistein", the principle objective of which is to determine the
mechanism(s) by which thetrihydroxyisoflavone genistein exerts its
chemopreventive effect against several types of cancer. Genistein and
thedihydroxyisoflavone daidzein are present in large quantities (2-3
mg/g) in soy, but are not found in other foods in theAmerican diet.
Women who eat a diet rich in soy foods have a much lower incidence of
breast cancer than those whoeat a typical American diet. Although
genistein has long been known for its weak estrogenic properties, it
has also beenshown in vitro to be an inhibitor of many protein
tyrosine kinases and to inhibit the growth of many cancer cell
lines,suggesting that it may have an important role in the prevention
of cancer. However, the crucial cellular targets of genistein in
its role as an anti-proliferative agent have not yet been identified.
The specific aims of this proposal are todetermine: (1) the
inhibitory effects of genistein on the serum-,estradiol- and EGF-
stimulated growth of a human breastcancer cell line with and without
expressed estrogen receptor; (2) whether genistein in human breast
cancer cell linesstimulated by growth factors inhibits the
phosphorylation of (a) the estrogen receptor, (b) the EGF receptor;
(c) keykinases in the signal transduction sequence activated by EGF;
(3) whether genistein suppresses the mitogenic inductionof expression
of the immediate early genes c-fos, c-jun and c-myc; (4) in a rat
model of breast cancer, whether dietarygenistein has a larger effect
when limited to the period from 25 days of age up to and during the
administration of thechemical carcinogen at 50 days of age (anti-
initiation effect), or after the first mammary tumors have begun to
appear(progression-promotion effect); (5) whether genistein
administered during puberty in female rats alters celldifferentiation
and proliferation in the mammary; and (6) whether inclusion of
genistein in the diet from puberty to timeof administration of DMBA
decreases the rate of formation and amount DMBA-DNA adducts in the
mammary. It isintended that this project should establish a rationale
basis for the use of soy as a recommended foodstuff to lower therisk
of cancer in Americans.
- References:
- Category: MODELS
- Subcategory: EXPOSURE AND RISK MODELS
- Keywords for Experimental System/Species: IN VITRO, HUMAN, MAMMALIAN (RAT), IN VIVO
- Keywords for Experimental Endpoints: FEMALE, GROWTH FACTORS, PUBERTY, CARCINOGENESIS
- Chemical Agents: SOY ISOFLAVONE GENISTEIN, PHYTOESTROGEN
- Performing Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM
- Contact: 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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