Effect of basic fibroblast growth factor on synthesis/secretion of pS2 protein by human breast cancer cells (MCF-7).
pS2 is an estrogen-induced mRNA species that was originally identified in the breast cancer cell line MCF-7. Exposure of the cells to basic fibroblast growth factor (bFGF) at the concentration of 10-100 ng/ml for 48-72 h resulted in a marked increase in the concentration of pS2 protein in the medium. The polymerase chain reaction with reverse transcriptase revealed that bFGF increased the amount of intracellular pS2 mRNA: immunocytochemical studies showed that exposure to the factor increased the amount of intracellular pS2 protein. Simultaneous addition of cycloheximide with bFGF completely abolished induction of pS2 protein, although it did not affect the induction of pS2 mRNA. Actinomycin D did not affect the stimulatory effect of bFGF on synthesis/secretion of pS2 protein. bFGF effectively abolished decay of the pS2 mRNA level caused by actinomycin D. These results suggest that the induction of the synthesis/secretion of pS2 protein by bFGF occurs at the post-transcriptional level, most probably due to the stabilization of pS2 mRNA. Another finding, that bFGF and estradiol have a synergistic effect on induction of pS2 protein, suggests the possibility that these two inducers act by a different but partly overlapping mechanism.
Department of Molecular Biology, Gifu Pharmaceutical University, Japan.
S
S
Miyashita
M
M
Hirota
T
T
Yamamoto
C
C
Shiroyama
Y
Y
Furukawa
K
K
Hayashi
D001943:Breast Neoplasms / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004357:Drug Synergism; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000378:metabolism; D011506:Proteins; D012333:RNA, Messenger / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D013256:Steroids; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D016222:Fibroblast Growth Factor 2; D003609:Dactinomycin; D004958:Estradiol; D003513:Cycloheximide