Functional interaction of fibroblast growth factor-8, bone morphogenetic protein and estrogen receptor in breast cancer cell proliferation

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12 Citations (Scopus)


Estrogen is involved in the development and progression of breast cancer. Here we investigated the effect of fibroblast growth factor (FGF)-8 on breast cancer cell proliferation caused by estrogen using human breast cancer MCF-7 cells. MCF-7 cells express estrogen receptor (ER)α, ERβ, FGF receptors, and Smad signaling molecules. Estradiol stimulated MCF-7 cell proliferation in a concentration-responsive manner, whereas BSA-bound estradiol had a weak effect on MCF-7 cell mitosis compared with the effect of free estradiol. It is notable that estrogen-induced cell proliferation was enhanced in the presence of FGF-8 and that the combined effects were reversed in the presence of an FGF-receptor kinase inhibitor or an ER antagonist. It was also revealed that FGF-8 increased the expression levels of ERα, ERβ and aromatase mRNAs, while estradiol reduced the expression levels of ERs, aromatase and steroid sulfatase in MCF-7 cells. FGF-8-induced phosphorylation of FGF receptors was augmented by estradiol, which was reversed by an ER antagonist. FGF-8-induced activation of MAPKs and AKT signaling was also upregulated in the presence of estrogen. On the other hand, FGF-8 suppressed BMP-7 actions that are linked to mitotic inhibition by activating the cell cycle regulator cdc2. FGF-8 was revealed to inhibit BMP receptor actions including Id-1 promoter activity and Smad1/5/8 phosphorylation by suppressing expression of BMP type-II receptors and by increasing expression of inhibitory Smads. Collectively, the results indicate that FGF-8 acts to facilitate cell proliferation by upregulating endogenous estrogenic actions as well as by suppressing BMP receptor signaling in ER-expressing breast cancer cells.

Original languageEnglish
Pages (from-to)7-17
Number of pages11
JournalMolecular and cellular endocrinology
Issue number1-2
Publication statusPublished - Aug 22 2011


  • Aromatase
  • Bone morphogenetic protein
  • Breast cancer
  • Estrogen receptor
  • Fibroblast growth factor
  • MAP kinase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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