The effect of endocrine therapy on fibroblast growth factor-like activity in nitrosomethylurea-induced rat mammary tumours.
Tumour regression following ovariectomy of rats bearing nitrosomethylurea-induced mammary tumours has been well characterised as a model for oestrogen receptor (ER)-positive breast cancer. We have shown that a similar regression response can be induced in these rats by the cytotoxic drug doxorubicin. Conditioned medium (CM) from serum-free explant cultures of the mammary tumours of ovariectomised rats showed a striking increase in its ability to transform NR6 cells compared to that of control or doxorubicin-treated rats (P = 0.001, t-test). Activity was also present in CM derived from rat uteri but not in ER-negative tissues such as skin and liver. Activity was further defined as fibroblast growth factor (FGF)-like by its strong affinity to heparin, partial neutralisation by antibodies to acidic FGF (aFGF) and partial co-elution with aFGF on salt elution from heparin. Both aFGF protein and mRNA were detected in tissue preparations of rat tumours and uterus.
Smith
J
J
Department of Anatomy, University of Cambridge, U.K.
Chander
S K
SK
Baillie
R
R
Coombes
R C
RC
D000818:Animals; D003470:Culture Media; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000187:drug effects / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008770:Methylnitrosourea; D010052:Ovariectomy; D051381:Rats; D014407:Tumor Cells, Cultured
D003470:Culture Media; D016220:Fibroblast Growth Factor 1; D008770:Methylnitrosourea; D004317:Doxorubicin; D006493:Heparin