Docosahexaenoic acid induces proteasome-dependent degradation of estrogen receptor α and inhibits the downstream signaling target in MCF-7 breast cancer cells

I. Fen Lu, Ann Che Hasio, Meng Chun Hu, Feng Ming Yang, Hui Min Su

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

About two thirds of breast cancers in women are hormone-dependent and require estrogen for growth, its effects being mainly mediated through estrogen receptor α (ERα). Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) have opposite effects on carcinogenesis, with DHA suppressing and AA promoting tumor growth both in vitro and in vivo. However, the mechanism is not clear. Here, we examined whether the effect is mediated through changes in ERα distribution. MCF-7 cells, an ERα-positive human breast cancer cell line, was cultured in estrogen-free medium containing 0, 10 or 60 μM DHA or AA, then were stimulated with estradiol. DHA supplementation resulted in down-regulation of ERα expression (particularly in the extranuclear fraction), a reduction in phosphorylated MAPK, a decrease in cyclin D1 levels and an inhibition in cell viability. In contrast, AA had no such effects. The DHA-induced decrease in ERα expression resulted from proteasome-dependent degradation and not from decreased ERα mRNA expression. We propose that breast cancer cell proliferation is inhibited by DHA through proteasome-dependent degradation of ERα, reduced cyclin D1 expression and inhibition of MAPK signaling.

Original languageEnglish
Pages (from-to)512-517
Number of pages6
JournalJournal of Nutritional Biochemistry
Volume21
Issue number6
DOIs
Publication statusPublished - Jun 1 2010
Externally publishedYes

Keywords

  • Arachidonic acid
  • Breast cancer
  • Cyclin D1
  • Docosahexaenoic acid
  • Estradiol
  • Estrogen receptor α
  • MAPK
  • Proteasome activity

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Medicine(all)

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