Fish oil alters tamoxifen-modulated expression of mRNAs that encode genes related to differentiation, proliferation, metastasis, and immune response in rat mammary tumors.
We have previously shown that a fish oil (FO)-rich diet increased the chemopreventive efficacy of tamoxifen (Tam) against N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinogenesis. Herein, we provide evidence that Tam treatment modifies gene expression of mammary tumors depending upon the type of dietary fat fed to the animals. Rats initiated with MNU and treated with Tam were fed a diet rich in corn oil or FO. After 8 wk, cribriform tumors were collected and gene expression analysis was performed. Increased RNA expression of genes such as SerpinB10, Wisp2, and Apod in tumors from FO-treated rats is indicative of highly differentiated tumors. Decreased expression of H19 and Igf2 mRNA in Tam-treated groups, and Gamma Synuclein mRNA in the FO + Tam group may be related to tumor growth impairment and lower metastatic capacity. Change in the expression of genes associated with immunity in animals in the FO + Tam group may suggest a shift in the immune response. These data show that, although Tam modulates the expression of genes leading to tumor growth impairment, further modulations of genes are influenced by FO. FO modulation of Tam changes in gene expression accounts for its enhancing chemopreventive effect against MNU-induced mammary carcinogenesis. Supplemental materials are available for this article. Go to the publisher's online edition of Nutrition and Cancer to view the supplemental file.
Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Lucas Tadeu
LT
Bidinotto
Ricardo López
RL
de Cicco
Johana Erika
JE
Vanegas
Julia
J
Santucci-Pereira
John Patrick
JP
Vanden Heuvel
Sharlene
S
Washington
Cesar
C
Aliaga
Haifang
H
Xu
Irma H
IH
Russo
Andrea
A
Manni
Karam
K
El-Bayoumy
Jose
J
Russo
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003314:Corn Oil / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic; D007109:Immunity; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008770:Methylnitrosourea / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015203:Reproducibility of Results; D013629:Tamoxifen / Q000494:pharmacology*; D059467:Transcriptome
D004041:Dietary Fats; D005395:Fish Oils; D012333:RNA, Messenger; D013629:Tamoxifen; D008770:Methylnitrosourea; D003314:Corn Oil