Identification of novel differentially expressed genes by the effect of a high-fat n-6 diet in experimental breast cancer.
In previous studies, we demonstrated that high corn oil diets promote the development of 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced mammary tumors. In this study, we have investigated whether modulation of gene expression is one of the mechanisms by which this high-fat diet exerts such effects. Female Sprague-Dawley rats were induced with DMBA and fed normolipidic (3% corn oil) or high-fat (20% corn oil) diet. Screening of genes differentially expressed in adenocarcinomas from the high corn oil diet group compared to the control diet group was performed with cDNA microarrays. The resulting six upregulated and nine downregulated genes were validated by Northern blot and/or reverse transcription (RT)-polymerase chain reaction (PCR). Further investigation in a higher number of adenocarcinomas showed that in the high-fat n-6 diet group, where the tumor phenotype was verified to be more aggressive, the expression of submaxillary gland alpha-2u globulin, vitamin D(3)-upregulated protein 1 (VDUP1), H19, and the unknown function gene that codifies the expressed sequence tag (EST)-Rn.32385 was significantly decreased in comparison with the control group (C). These results, together with the fact that VDUP1, H19, and this globulin have been associated with cell proliferation and differentiation, open a new line of research about how the underexpression of these genes contributes to the stimulating effect of a high corn oil diet on experimental mammary carcinogenesis.
Escrich
Eduard
E
Department of Cell Biology, Physiology and Immunology, Physiology Unit, Medical School, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Moral
Raquel
R
García
Gemma
G
Costa
Irmgard
I
Sánchez
Josep Anton
JA
Solanas
Montserrat
M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000510:Alpha-Globulins / Q000187:drug effects / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D002273:Carcinogens / Q000633:toxicity; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics; D003314:Corn Oil; D004041:Dietary Fats / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013879:Thioredoxins; D051020:bcl-X Protein
D000510:Alpha-Globulins; C494813:Bcl2l1 protein, rat; D002273:Carcinogens; D002352:Carrier Proteins; D004041:Dietary Fats; D043371:Fatty Acids, Omega-6; C094335:H19 long non-coding RNA; D019253:Proto-Oncogene Proteins c-bcl-2; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C486715:TXNIP protein, human; C013803:alpha 2u globulin; D051020:bcl-X Protein; D013879:Thioredoxins; D015127:9,10-Dimethyl-1,2-benzanthracene; D003314:Corn Oil