Effect of ω-6 polyunsaturated fatty acid (linoleic acid) on BRCA1 gene expression in MCF-7 cell line

Kachhap, Sushant K.; Dange, Prerana; Ghosh, Soumendra N.

doi:10.1016/s0304-3835(00)00371-2

Cited by 23 publications

(13 citation statements)

References 20 publications

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“…Furthermore, dietary lipids have also been shown to affect the expression of the suppressor genes BRCA1 and BRCA2. Thus, LA and oestradiol exerted a synergistic effect on the gene expression of BRCA1 in MCF-7 tumor cells, as they decreased the mRNA levels of this gene compared with controls or with cells treated with LA or oestradiol alone [111]. On the contrary, in MCF-7 and MDA-MB231 tumor cell lines treatment with n-3 PUFA (EPA and DHA) increased the BRCA1 and BRCA2 mRNA expression, but no effects were observed with n-6 PUFA (AA) treatment [112].…”

Section: Regulation Of Gene Expressionmentioning

confidence: 93%

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

Escrich

Moral

Grau

et al. 2007

Molecular Nutrition Food Res

125

105

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Cancer is one of the main causes of mortality worldwide. Geographical differences in incidence rates suggest a key effect of environmental factors, especially diet, in its aetiology. Epidemiologic and experimental studies have found a role of dietary lipids in cancer, particularly breast, colorectal, and prostate cancers. Their incidence in the Mediterranean countries, where the main source of fat is olive oil, is lower than in other areas of the world. Human studies about the effects of dietary lipids are little conclusive, probably due to methodological issues. On the other hand, experimental data have clearly demonstrated that the influence of dietary fats on cancer depends on the quantity and the type of lipids. Whereas a high intake of n-6 PUFA and saturated fat has tumor-enhancing effects, n-3 PUFA, conjugated linoleic acid and gamma-linolenic acid have inhibitory effects. Data regarding MUFA have not always been conclusive, but high olive oil diets seem to have protective effects. Such effects can be due to oleic acid, the main MUFA in olive oil, and to certain minor compounds such as squalene and phenolic compounds. This work aims to review the current knowledge about the relationship between dietary lipids and cancer, with a special emphasis on olive oil, and the molecular mechanisms underlying these effects: modifications on the carcinogenesis stages, hormonal status, cell membrane structure and function, signal transduction pathways, gene expression, and immune system.

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Section: Regulation Of Gene Expressionmentioning

confidence: 93%

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

Escrich

Moral

Grau

et al. 2007

Molecular Nutrition Food Res

125

105

View full text Add to dashboard Cite

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“…Results for the pools of transformants were described, and those for the single cell clones were substantially the same. The MCF-7 cell line contains a single normal allele of BRCA1 (48).…”

Section: Methodsmentioning

confidence: 99%

BRCA1 Suppresses Osteopontin-mediated Breast Cancer

El‐Tanani

Campbell

Crowe

et al. 2006

Journal of Biological Chemistry

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BRCA1 is a well described breast cancer susceptibility gene thought to be involved primarily in DNA repair. However, mutation within the BRCA1 transcriptional domain is also implicated in neoplastic transformation of mammary epithelium, but responsible mechanisms are unclear. Here we show in a rat mammary model system that wild type (WT) BRCA1 specifically represses the expression of osteopontin (OPN), a multifunctional estrogen-responsive gene implicated in oncogenic transformation, particularly that of the breast. WT.BRCA1 selectively binds OPN-activating transcription factors estrogen receptor ␣, AP-1, and PEA3, inhibits OPN promoter transactivation, and suppresses OPN mRNA and protein both from an endogenous gene and a relevant model inducible gene. WT.BRCA1 also inhibits OPN-mediated neoplastic transformation characterized by morphology change, anchorage-independent growth, adhesion to fibronectin, and invasion through Matrigel. A mutant BRCA1 allele (Mut.BRCA1) associated with familial breast cancer lacks OPN suppressor effects, binds to WT.BRCA1, and impedes WT.BRCA1 suppression of OPN. Stable transfection of rat breast tumor cell lines with Mut.BRCA1 dramatically up-regulates OPN protein and induces anchorageindependent growth. In human primary breast cancer, BRCA1 mutation is significantly associated with OPN overexpression. Taken together, these data suggest that BRCA1 mutation may confer increased tissue-specific cancer risk, in part by disruption of BRCA1 suppression of OPN gene transcription.

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“…a combination of linoleic acid bovine serum conjugate (LA) and E2 or DHA or both LA 1 E2 1 DHA. The concentration of LA (1 mg/ml) and E2 (10 nM/ml) was used as described by Kachhap et al 18 and DHA (1.5 mg/ml) as described by Rose et al 19 …”

Section: Cell Culturementioning

confidence: 99%

“…6 Recently, we have demonstrated that v-6 fatty acid linoleic acid (LA) in presence of estradiol (E2) enhances proliferation and activity and anchorage independent growth with down regulation of BRCA1 mRNA expression in MCF-7 cell line. 18 Since v-3 fatty acid (docosahexanoic acid, DHA) is shown to block the promoting effect of v-6 polyunsaturated fatty acid (LA), we wanted to see whether addition of DHA can inhibit the growth of MCF-7 cells which are exposed to LA 1 E2. Further, since BRCA1 mRNA was found to be down regulated in LA treated culture, whether any alteration of mRNA could be seen in DHA treated culture.…”

Section: Introductionmentioning

confidence: 99%

Effect of ω-3 Fatty Acid (Docosahexanoic Acid) on BRCA1 Gene Expression and Growth in MCF-7 Cell Line

Kachhap

Dange

Santani

et al. 2001

Cancer Biotherapy and Radiopharmaceuticals

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Recently, we have demonstrated that omega-6 fatty acid linoleic acid (LA) in presence of estradiol (E2) enhances proliferation and anchorage independent growth with down regulation of BRCA1 mRNA expression in MCF-7 cell line. Since omega-3 fatty acid (docosahexanoic acid, DHA) is known to block the promoting effect of omega-6 polyunsaturated fatty acid (LA), we wanted to see whether addition of DHA can inhibit the growth of MCF-7 cells which are exposed to LA + E2 and any alteration of BRCA1 mRNA expression could be seen in DHA treated culture. Experiments on MCF-7 cells with DHA revealed both decrease in proliferation and anchorage independency as compared to controls; while no change of BRCA1 mRNA expression was observed. Further, when DHA was administered to cells along with LA + E2, no change in BRCA1 expression was observed, however, a marked decrease in proliferation and soft agar colony formation was evident, indicating inhibition of MCF-7 cells following DHA treatment. Flow cytometric analysis showed that DHA treated cells either alone or in combination with LA + E2 induced marked G1/S and G2/M arrest of the cells, suggesting the inhibitory effect of DHA at this phase of cell cycle. However, neither typical DNA ladder nor fragmented nuclei or apoptotic bodies were observed, ruling out presence of apoptosis following DHA treatment.

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Effect of ω-6 polyunsaturated fatty acid (linoleic acid) on BRCA1 gene expression in MCF-7 cell line

Cited by 23 publications

References 20 publications

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

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

BRCA1 Suppresses Osteopontin-mediated Breast Cancer

Effect of ω-3 Fatty Acid (Docosahexanoic Acid) on BRCA1 Gene Expression and Growth in MCF-7 Cell Line

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