Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c

Yu An Yang, Patrice J. Morin, Wan Fang Han, Tinghua Chen, Daniel M. Bornman, Edward Gabrielson, Ellen S. Pizer

Research output: Contribution to journalArticle

Abstract

Activation of fatty acid synthase (FAS) expression and fatty acid synthesis is a common event in human breast cancer. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate genes involved in lipid metabolism, including FAS. SREBP-1c expression is induced in liver and adipose tissue by insulin and by fasting/refeeding and is critical for nutritional regulation of lipogenic gene expression. In contrast, upregulation of fatty acid metabolism during in vitro transformation of human mammary epithelial cells and in breast cancer cells was driven by increased MAP kinase and PI 3-kinase signaling, which increased SREBP-1 levels. SREBP-1a was more abundant than SREBP-1c in many proliferative tissues and cultured cells and was thus a candidate to regulate lipogenesis for support of membrane synthesis during cell growth. We now show that SREBP-1c and FAS mRNA were both increased by H-ras transformation of MCF-10a breast epithelial cells and were both reduced by exposure of MCF-7 breast cancer cells to the MAP kinase inhibitor, PD98059, or the PI 3-kinase inhibitor, wortmannin, while SREBP-1a and SREBP-2 showed less variation. Similarly, the mRNA levels for FAS and SREBP-1c in a panel of primary human breast cancer samples showed much greater increases than did those for SREBP-1a and SREBP-2 and were significantly correlated with each other, suggesting coordinate regulation of SREBP-1c and FAS in clinical breast cancer. We conclude that regulation of FAS expression in breast cancer is achieved through modulation of SREBP-1c, similar to the regulation in liver and adipose tissue, although the upstream regulation of liopgenesis differs in these tissues.

Original languageEnglish (US)
Pages (from-to)132-137
Number of pages6
JournalExperimental Cell Research
Volume282
Issue number2
DOIs
StatePublished - Jan 15 2003

Fingerprint

Sterol Regulatory Element Binding Protein 1
Fatty Acid Synthases
Breast Neoplasms
Sterol Regulatory Element Binding Protein 2
Phosphatidylinositol 3-Kinases
Adipose Tissue
Breast
Fatty Acids
Epithelial Cells
Sterol Regulatory Element Binding Proteins
MAP Kinase Kinase 3
Messenger RNA
Lipogenesis
Liver
Gene Expression Regulation
Lipid Metabolism
Cultured Cells
Fasting
Transcription Factors
Phosphotransferases

Keywords

  • Breast cancer
  • EGF
  • Fatty acid synthase
  • MAP kinase
  • PI 3-kinase
  • Real-time RT-PCR
  • SREBP-1c

ASJC Scopus subject areas

  • Cell Biology

Cite this

Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c. / Yang, Yu An; Morin, Patrice J.; Han, Wan Fang; Chen, Tinghua; Bornman, Daniel M.; Gabrielson, Edward; Pizer, Ellen S.

In: Experimental Cell Research, Vol. 282, No. 2, 15.01.2003, p. 132-137.

Research output: Contribution to journalArticle

Yang, Yu An ; Morin, Patrice J. ; Han, Wan Fang ; Chen, Tinghua ; Bornman, Daniel M. ; Gabrielson, Edward ; Pizer, Ellen S. / Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c. In: Experimental Cell Research. 2003 ; Vol. 282, No. 2. pp. 132-137.
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AU - Yang, Yu An

AU - Morin, Patrice J.

AU - Han, Wan Fang

AU - Chen, Tinghua

AU - Bornman, Daniel M.

AU - Gabrielson, Edward

AU - Pizer, Ellen S.

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AB - Activation of fatty acid synthase (FAS) expression and fatty acid synthesis is a common event in human breast cancer. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate genes involved in lipid metabolism, including FAS. SREBP-1c expression is induced in liver and adipose tissue by insulin and by fasting/refeeding and is critical for nutritional regulation of lipogenic gene expression. In contrast, upregulation of fatty acid metabolism during in vitro transformation of human mammary epithelial cells and in breast cancer cells was driven by increased MAP kinase and PI 3-kinase signaling, which increased SREBP-1 levels. SREBP-1a was more abundant than SREBP-1c in many proliferative tissues and cultured cells and was thus a candidate to regulate lipogenesis for support of membrane synthesis during cell growth. We now show that SREBP-1c and FAS mRNA were both increased by H-ras transformation of MCF-10a breast epithelial cells and were both reduced by exposure of MCF-7 breast cancer cells to the MAP kinase inhibitor, PD98059, or the PI 3-kinase inhibitor, wortmannin, while SREBP-1a and SREBP-2 showed less variation. Similarly, the mRNA levels for FAS and SREBP-1c in a panel of primary human breast cancer samples showed much greater increases than did those for SREBP-1a and SREBP-2 and were significantly correlated with each other, suggesting coordinate regulation of SREBP-1c and FAS in clinical breast cancer. We conclude that regulation of FAS expression in breast cancer is achieved through modulation of SREBP-1c, similar to the regulation in liver and adipose tissue, although the upstream regulation of liopgenesis differs in these tissues.

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KW - EGF

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KW - PI 3-kinase

KW - Real-time RT-PCR

KW - SREBP-1c

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