Diet-gene interactions in estrogen-induced mammary carcinogenesis in the ACI rat.
It is well accepted that hormonal, dietary and genetic factors each influence breast cancer risk. However, the underlying mechanisms and the extent to which these factors interact are largely unknown. We have demonstrated that the female ACI rat exhibits a unique genetically conferred propensity to develop mammary cancers when treated with physiological levels of 17beta-estradiol (E2). More recently, we have mapped to rat chromosome 5 a strong genetic modifier of susceptibility to E2-induced mammary cancers, termed estrogen-induced mammary cancer 1 (Emca1), and have identified potential Emca1 candidate genes. Because estrogens have been inextricably linked to the genesis of breast cancer in humans, the ACI rat model has the potential to reveal novel physiologically relevant insights into how the contributory actions of E2 are modified by specific dietary factors. In the present study, we have examined the ability of a 40% restriction of dietary energy consumption to inhibit E2-induced mammary carcinogenesis. The hypothesis tested was that energy restriction will inhibit mammary carcinogenesis even when circulating E2 remains elevated through administration of exogenous hormone. The data presented herein strongly suggest that energy restriction inhibits E2-induced mammary carcinogenesis in the ACI rat at least partly by retarding progression of atypical hyperplastic foci to carcinoma.
Harvell
D M
DM
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE, USA.
Strecker
T E
TE
Xie
B
B
Buckles
L K
LK
Tochacek
M
M
McComb
R D
RD
Shull
J D
JD
D000818:Animals; D001835:Body Weight; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004038:Diet, Reducing; D004195:Disease Models, Animal; D002149:Energy Intake; D004958:Estradiol / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D009376:Neoplasms, Hormone-Dependent / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D011912:Rats, Inbred ACI
D004958:Estradiol