Insulin and estrogen receptor ligand influence the FGF-2 activities in MCF-7 breast cancer cells.
From the MCF-7 cell line we have developed, a human mammary cancer cell subline with the same karyotype as the mother strain and named MCF-7(SF), able to grow in serum-free chemically defined medium. This cell subline was firstly used to analyze the effect of basic fibroblast growth factor (FGF-2) in estrogen-receptor-positive human breast cancer cells. FGF-2 like estradiol is able to increase cell proliferation and pS2 expression but was also found to inhibit progesterone receptor (PR) expression. The anti-estrogen tamoxifen partly counteracts the effects of FGF-2 and to discriminate between its two main mediators (estrogen receptor vs. anti-estrogen binding site, AEBS) we compare the efficacies of pure anti-estrogen (ICI 182,780) and AEBS ligand (PBPE). It appears that pure anti-estrogen counteracts cell growth and pS2 effects of FGF-2 since AEBS ligand inhibits the cell growth but has no activity on pS2 expression. Secondly, adding insulin (10(-6)M) in the culture medium induces a strong increase in cell proliferation, which then elicits an inhibitory effect of FGF-2 and addition of anti-estrogens, are less efficient to further decrease growth, since the effects of FGF-2 and anti-estrogens on pS2 expression are conserved.
Garnier
Martine
M
Département Innovation Therapeutique et Oncology INSERM U 563, Institut C. Regaud, 20-24 rue du pont Saint Pierre, Toulouse Cedex 31052, France.
Giamarchi
Claire
C
Delrieu
Isabelle
I
Rio
Marie-Christine
MC
Chinestra
Patrick
P
Bayard
Francis
F
Poirot
Marc
M
Faye
Jean-Charles
JC
D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008024:Ligands; D014176:Protein Biosynthesis; D011506:Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D011960:Receptors, Estrogen / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011980:Receptors, Progesterone / Q000096:biosynthesis; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D007328:Insulin; D008024:Ligands; D011506:Proteins; D011960:Receptors, Estrogen; D017468:Receptors, Fibroblast Growth Factor; D011980:Receptors, Progesterone; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D016222:Fibroblast Growth Factor 2; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2