title: Differential expression of FGF family members in a progestin-dependent BT-474 human breast cancer xenograft model.
abstract: Members of the fibroblast growth factor (FGF) family have been associated with tumor progression and angiogenesis, though the mechanism through which they affect the progression of breast cancer remains elusive. We recently showed that progestins increase the production of the potent angiogenic factor VEGF in an in vivo BT-474 human breast cancer cell-derived xenograft model. In this study we sought to determine the effect of progesterone (P) on regulation of specific FGF family members (FGF-2, FGF-4 and FGF-8) in the same model. Using immunohistochemistry we found that treatment with P significantly reduced FGF-2 and FGF-8 levels, while modestly increasing the levels of FGF-4 in tumors collected at the termination of the study or soon after P treatment began. The in vivo observations with FGF-2 were confirmed in cultured BT-474 cells, though the P-mediated reduction in FGF-2 was not blocked by the anti-progestin RU-486, suggesting that classical progesterone receptors (PR) are not involved in FGF-2 down-regulation. Also, P did not affect levels of FGF-2 mRNA in BT-474 cells, indicating that P exerts its effects on FGF-2 post-transcriptionally. Our observations suggest that the in vivo stimulation of BT-474 cell growth by P is associated with down-regulation of FGF-2 and FGF-8. Furthermore, since FGF-4 levels increased during P-treatment, FGF-4 may be required for tumor growth and maintenance and might therefore be a potential therapeutic target through which to suppress P-dependent tumor growth.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, USA.
authors.forename: Franklin R
authors.initials: FR
authors.lastname: López Pérez
authors.forename: Yayun
authors.initials: Y
authors.lastname: Liang
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Besch-Williford
authors.forename: Benford
authors.initials: B
authors.lastname: Mafuvadze
authors.forename: Salman M
authors.initials: SM
authors.lastname: Hyder
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D051519:Fibroblast Growth Factor 4 / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D011374:Progesterone / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous; D047368:Tumor Burden
chemical_list: C496445:FGF4 protein, human; C496456:FGF8 protein, human; D051519:Fibroblast Growth Factor 4; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D051524:Fibroblast Growth Factor 8; D011374:Progesterone; D005346:Fibroblast Growth Factors