title: Dietary energy restriction inhibits estrogen-induced mammary, but not pituitary, tumorigenesis in the ACI rat.
abstract: Because of the suggested role of energy consumption and the well-documented role of estrogens in the etiology of breast cancer, we have examined the effect of a 40% restriction of dietary energy consumption on the ability of administered 17beta-estradiol (E2) to induce mammary tumorigenesis in female ACI rats. Experiments herein test the hypothesis that at least part of the inhibitory effect of energy restriction on mammary tumorigenesis is exerted downstream of potential effects of dietary manipulation on the production of estrogens by the ovaries. Ovary-intact ACI rats were fed a control or a 40% energy-restricted diet and were either treated continuously with E2 from subcutaneous Silastic tubing implants or received no hormone treatment. Mammary cancers rapidly developed in E2-treated rats fed the control diet; within 216 days of initiation of E2 treatment 100% of the population at risk exhibited palpable mammary tumors. Dietary energy restriction markedly inhibited E2-induced mammary tumorigenesis, as evidenced by significant reductions in cancer incidence and tumor burden as well as a significant increase in the latency to the appearance of the first palpable cancer. The inhibitory actions of dietary energy restriction on E2-induced mammary tumorigenesis were associated with an inhibition of E2-stimulated mammary cell proliferation. However, this inhibition was insufficient to block induction of lobuloalveolar hyperplasia or appearance of focal regions of atypical epithelial hyperplasia. These data suggest that dietary energy restriction inhibits E2-induced mammary cancer by attenuating or retarding the progression of atypical hyperplasia to carcinoma. Expression of progesterone receptor (PR) was up-regulated within the focal regions of atypical hyperplasia and the carcinomas induced by E2, regardless of whether the rats were fed the control or energy-restricted diet. However, circulating progesterone was reduced by dietary energy restriction, suggesting a possible mechanism for inhibition of mammary tumorigenesis. Dietary energy restriction did not inhibit the ability of administered E2 to induce prolactin (PRL)-producing pituitary tumors and associated hyperprolactinemia, indicating that the inhibitory effects of dietary energy restriction on mammary tumorigenesis are tissue specific and independent of circulating E2 and PRL.
authors.affiliation: Eppley Institute for Research in Cancer, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.
authors.forename: Djuana M E
authors.initials: DM
authors.lastname: Harvell
authors.forename: Tracy E
authors.initials: TE
authors.lastname: Strecker
authors.forename: Benjamin
authors.initials: B
authors.lastname: Xie
authors.forename: Karen L
authors.initials: KL
authors.lastname: Pennington
authors.forename: Rodney D
authors.initials: RD
authors.lastname: McComb
authors.forename: James D
authors.initials: JD
authors.lastname: Shull
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000473:pathology; D002149:Energy Intake / Q000187:drug effects; D004967:Estrogens / Q000097:blood / Q000494:pharmacology*; D005508:Food Deprivation; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000473:pathology*; D010911:Pituitary Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D011374:Progesterone / Q000097:blood / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011912:Rats, Inbred ACI; D013997:Time Factors
chemical_list: D004967:Estrogens; D011374:Progesterone; D011388:Prolactin