Identification of novel differentially expressed genes by the effect of a high‐fat n‐6 diet in experimental breast cancer

Abstract

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.

Molecular mechanisms of the effects of olive oil and other dietary lipids on cancer

“…These genes, identified and validated, were submaxillary gland a-2u globulin, vitamin D3-upregulated protein 1, the paternally imprinted gene H19 and the unknown expressed sequence tag Rn.32385. Tumors from high n-6 fat diet animals, showing downregulation of these genes, were associated with clinical behavior and anatomopathological features of higher malignancy than control tumors [115]. Moreover, the expression of these genes was not modified by the effect of a high virgin olive oil diet.…”

High corn oil and extra virgin olive oil diets and experimental mammary carcinogenesis: clinicopathological and immunohistochemical p21Ha-Ras expression study

“…In this model, we have previously demonstrated a tumour-enhancing effect of a high corn oil diet and a negative modulatory effect of a high extra virgin olive oil diet on clinical mammary carcinogenesis and on the histopathological features of the carcinomas [18,19]. We have also investigated several molecular mechanisms to gain insight into the complex pathways underlying these modulatory effects [20][21][22][23][24][25][26][27]. In this sense, we recently showed that high extra virgin olive oil diet decreases Ras activity, while high corn oil diet stimulates breast cancer without affecting Ras-cell signalling pathways [28].…”

Thioredoxin and Thioredoxin Target Proteins: From Molecular Mechanisms to Functional Significance

“…Higher Txnip expression levels are associated with better prognosis in breast cancer patients as measured by the metastasis-free interval after initial treatment (31). Txnip down-regulation promotes carcinogenesis, and Txnip is downregulated in many different forms of cancer, including breast, prostate, colorectal, gastric, kidney, liver cancer, squamous cell carcinoma, melanoma, pheochromocytoma, HTLV-1 infected T cells, B-cell and Hodgkin lymphoma, and acute lymphoblastic and chronic lymphocytic leukemia (4,73,77,82,93,158,193,210,217,273,276,278,296,304,307).…”