Interferons alpha and beta down-regulate the expression of basic fibroblast growth factor in human carcinomas.
We investigated the influence of interferons alpha, beta, and gamma (IFN-alpha, -beta, and -gamma) on the production of basic fibroblast growth factor (bFGF) by human renal carcinoma cells. The human renal carcinoma cell metastatic line SN12PM6 was established in culture from a lung metastasis and SN12PM6-resistant cells were selected in vitro for resistance to the antiproliferative effects of IFN-alpha or IFN-beta. IFN-alpha and IFN-beta, but not IFN-gamma, down-regulated the expression of bFGF at the mRNA and protein levels by a mechanism independent of their antiproliferative effects. Down-regulation of bFGF required a long exposure (> 4 days) of cells to low concentrations (> 10 units/ml) of IFN-alpha or IFN-beta. The withdrawal of IFN-alpha or IFN-beta from the medium permitted SN12PM6-resistant cells to resume production of bFGF. The incubation of human bladder, prostate, colon, and breast carcinoma cells with noncytostatic concentrations of IFN-alpha or IFN-beta also produced down-regulation of bFGF production.
Singh
R K
RK
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Gutman
M
M
Bucana
C D
CD
Sanchez
R
R
Llansa
N
N
Fidler
I J
IJ
D001483:Base Sequence; D015152:Blotting, Northern; D002292:Carcinoma, Renal Cell / Q000556:secondary; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D017403:In Situ Hybridization; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007680:Kidney Neoplasms; D007700:Kinetics; D008175:Lung Neoplasms / Q000556:secondary; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D016899:Interferon-beta