PRODUCTION AND ESTROGEN REGULATION OF FGF1 IN NORMAL AND CANCER BREAST CELLS

To investigate the relationship between the FGF1 oestrogen regulation and the normal/cancer status of breast cells, we have studied FGF1 17 beta-oestradiol regulation in normal, transformed and cancerous cells. Normal (NMEC), transformed (HBL-100) and cancerous (MCF-7, MDA-MB-231 ) human mammary epithelial cells express different levels of FGF1 mRNA s, Western blot analysis allowed us to characterize FGF1 as an 18 kDa form of this polypeptide. Using a neutralizing anti-FGF1 antibody we d emonstrated that FGF1 is secreted by all mammary cells studied and sti mulates their proliferation in an autocrine manner, We have examined t he regulation of FGF1 mRNAs in response to 17 beta-oestradiol. FGF1 mR NAs were upregulated in hormone-dependent NMEC but was not upregulated either in hormone-sensitive HBL-100 cells or in the hormone-dependent cancerous cell line MCF-7, However, enzyme linked immunosorbent assay indicated an increase of FGF1 protein in NMEC, HBL-100 and MCF-7 cell s. We have also examined the 17 beta-oestradiol regulation of the four alternatively spliced FGF1 mRNAs: 1.A, 1.B, 1.C: and 1.D, Only 1.B tr anscripts were downregulated by 17 beta-oestradiol in normal cells. Th ese results show that 17 beta-oestradiol regulates FGF1 mRNAs in a cel l-specific manner, and that this regulation may be transcriptional or translational depending on cell phenotype. The specificity of oestradi ol effects was checked using its receptor antagonist tamoxifen. (C) 19 98 Elsevier Science B,V.