J Breast Cancer.  2007 Jun;10(2):127-133. 10.4048/jbc.2007.10.2.127.

The Effects of Genistein to Expression of Fatty Acid Synthase in Breast Cancer Cells

Affiliations
  • 1Department of Surgery, Koyang University Hospital, Daejeon, Korea. dsyoonmd@kyuh.co.kr
  • 2Department of Urology, Koyang University Hospital, Daejeon, Korea.
  • 3Myung-gok Research Institute for Medical Science, Koyang University Hospital, Daejeon, Korea.

Abstract

PURPOSE: The relatively low incidence of breast cancer in Asian countries with cultures which traditionally eat a large amount of soy is worth noticing in research fields. Genistein is a isoflavone phytoestrogen found in soy and its consumption may have a role in cancer etiology. We have established a hypothesis that a diet high in soy consumption is related to a low incidence of breast cancer. Fatty acid synthase (FAS) is a multi-protein enzyme responsible for de novo biosynthesis of fatty acids. Recent studies have demonstrated that high levels of FAS occurs in a subset of human cancers, such as breast cancer, ovarian cancer, and prostate cancer. High level of FAS are associated with a poor prognosis. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate genes involved in lipid metabolism, including FAS. Recent studies show that expression of SREBP1c is correlates with FAS expression. The aim of this study is to investigate the effect of genistein on the expression of FAS in breast cancer cells.
METHODS
We performed immunofluorescent staining to examine the expression of FAS under different concentration of genistein. RT-PCR was also performed to investigate the mRNA expression of FAS and SREBP1c in different conditioned breast cancer cells treated with different concentration of FAS inhibitor and genistein.
RESULTS
By immunofluorescent staining, the FAS expression after treatment with the FAS inhibitor, C75, decreased at a micron10 M concentration. However the expression of FAS decreased at all concentrations of genistein (0.5, 1, 5, 10 micronM). The mRNA levels of FAS and SREBP1c after treatment with C75 decreased constantly according to time and concentration. However the effect was noted only after 12 hr. The mRNA level of FAS and SREBP1c following treatment with genistein decreased at only a 10 micronM concentration (p<0.005).
CONCLUSION
Genistein may down regulate FAS expression in breast cancer cells through modulation of SREBP-1c. This finding may account for the relatively low incidence of breast cancer in Asians who consume a large amount of soy in their diet.

Keyword

Breast cancer; FAS; Genistein; SREBPs

MeSH Terms

Asian Continental Ancestry Group
Breast Neoplasms*
Breast*
Diet
Fatty Acids
Genistein*
Humans
Incidence
Lipid Metabolism
Ovarian Neoplasms
Phytoestrogens
Prognosis
Prostatic Neoplasms
RNA, Messenger
Sterol Regulatory Element Binding Protein 1
Sterol Regulatory Element Binding Proteins
Transcription Factors
Fatty Acids
Genistein
Phytoestrogens
RNA, Messenger
Sterol Regulatory Element Binding Protein 1
Sterol Regulatory Element Binding Proteins
Transcription Factors

Figure

  • Fig 1 Expression of FAS with immunofluorescent staining.

  • Fig 2 Expression of FAS in MDA-MB-231 cell line according to drugs.

  • Fig 3 Expression of FAS and SREBP-1c mRNA according to concentrations of FAS inhibitor (C75) and genistein.

  • Fig 4 Expression of FAS mRNA according to concentrations of FAS inhibitor (C75) and genistein. The mRNA levels of FAS after treatment with C75 decreased constantly according to time and concentration. However the effect was noted only after 12 hr. The mRNA level of FAS following treatment with genistein decreased at only a 10 µM concentration (Kruskal-Wallis Test p<0.05; Mann-Whitney test p<0.05 in C75, Kruskal-Wallis Test p<0.05 in Genistin (10 µM); Mann-Whitney test p<0.05 in genistein).

  • Fig 5 Expression of SREBP-1c mRNA according to concentrations of FAS inhibitor (C75) and genistein. The mRNA levels of SREBP1c after treatment with C75 decreased constantly according to time and concentration. The mRNA level of SREBP1c following treatment with genistein decreased at only a 10 µM concentration (p<0.005) (Kruskal-Wallis Test p>0.05 in C75; Kruskal-Wallis Test p<0.05 in C75, Mann-Whitney test p<0.05 in genistein 10 µM).


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