MAMMARY-GLAND FACTOR-ACTIVATED BY PROLACTIN IN MAMMARY EPITHELIAL-CELLS AND ACUTE-PHASE RESPONSE FACTOR-ACTIVATED BY INTERLEUKIN-6 IN LIVER-CELLS SHARE DNA-BINDING AND TRANSACTIVATION POTENTIAL

被引:68
作者
STANDKE, GJR
MEIER, VS
GRONER, B
机构
[1] TUMOR BIOL CTR, INST EXPTL CANC RES, D-79106 FREIBURG, GERMANY
[2] FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
关键词
D O I
10.1210/me.8.4.469
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We have studied transcription factors that are coupled to the activation of cytokine receptors in liver and in mammary epithelial cells. Interleukin-6 (IL-6) causes the rapid activation of the acute-phase response factor (APRF) in the liver of animals during acute inflammation and in cultured human hepatoma cells (HepG2) and induces the transcription of the acute-phase protein genes, e.g. alpha(2)-macroglobulin (alpha(2)-M). In the mammary gland and in cultured HC11 mammary epithelial cells, milk protein genes, e.g. beta-casein, are induced by the lactogenic hormones, insulin, glucocorticoids, and PRL. The induction of the beta-casein gene promoter is preceded by the activation of the mammary gland factor (MGF). We have compared the DNA binding sequences of APRF and MGF, 5'-CTTCTT/GGGAATT-3', and have found that they coincide in 11 of 12 positions. Bandshift experiments and oligonucleotide competition experiments showed that both factors, MGF and APRF, are able to bind to the IL-6 response element of the alpha(2)-M gene promoter and to the lactogenic hormone response element of the a-casein gene promoter with very similar specificities. Partial proteolytic digestion of APRF and MGF DNA complexes yielded similar clipping patterns. The UV cross-linked DNA complexes of both transcription factors were of the same apparent molecular mass. IL-6 activation of APRF in HepG2 cells can be observed within minutes. MGF induction by PRL in HC11 cells occurs with similar kinetics. The synergistic action of glucocorticoids and PRL is necessary for the induction of the beta-casein gene, but PRL is sufficient for MGF activation. Multimers of the MGF binding site confer IL-6 inducibility to a reporter gene in transiently transfected HepG2 cells. We conclude that the IL-6 receptor in liver and the PRL receptor in the mammary gland activate very similar transcription factors.
引用
收藏
页码:469 / 477
页数:9
相关论文
共 32 条
[1]   INTERACTION OF 2 SEQUENCE-SPECIFIC SINGLE-STRANDED DNA-BINDING PROTEINS WITH AN ESSENTIAL REGION OF THE BETA-CASEIN GENE PROMOTER IS REGULATED BY LACTOGENIC HORMONES [J].
ALTIOK, S ;
GRONER, B .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (12) :7303-7310
[2]  
Ausubel FM., 1995, MOL REPROD DEV, V3rd edn, DOI DOI 10.1002/MRD.1080010210
[3]   PROLACTIN REGULATION OF BETA-CASEIN GENE-EXPRESSION AND OF A CYTOSOLIC 120-KD PROTEIN IN A CLONED MOUSE MAMMARY EPITHELIAL-CELL LINE [J].
BALL, RK ;
FRIIS, RR ;
SCHOENENBERGER, CA ;
DOPPLER, W ;
GRONER, B .
EMBO JOURNAL, 1988, 7 (07) :2089-2095
[4]   HEMATOPOIETIC RECEPTORS AND HELICAL CYTOKINES [J].
BAZAN, JF .
IMMUNOLOGY TODAY, 1990, 11 (10) :350-354
[5]   LIFR-BETA AND GP-130 AS HETERODIMERIZING SIGNAL TRANSDUCERS OF THE TRIPARTITE CNTF RECEPTOR [J].
DAVIS, S ;
ALDRICH, TH ;
STAHL, N ;
PAN, L ;
TAGA, T ;
KISHIMOTO, T ;
IP, NY ;
YANCOPOULOS, GD .
SCIENCE, 1993, 260 (5115) :1805-1808
[6]   FIREFLY LUCIFERASE GENE - STRUCTURE AND EXPRESSION IN MAMMALIAN-CELLS [J].
DEWET, JR ;
WOOD, KV ;
DELUCA, M ;
HELINSKI, DR ;
SUBRAMANI, S .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (02) :725-737
[7]   PROLACTIN AND GLUCOCORTICOID HORMONES SYNERGISTICALLY INDUCE EXPRESSION OF TRANSFECTED RAT BETA-CASEIN GENE PROMOTER CONSTRUCTS IN A MAMMARY EPITHELIAL-CELL LINE [J].
DOPPLER, W ;
GRONER, B ;
BALL, RK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (01) :104-108
[8]   SYNERGISTIC ACTION OF INTERLEUKIN-6 AND GLUCOCORTICOIDS IS MEDIATED BY THE INTERLEUKIN-6 RESPONSE ELEMENT OF THE RAT ALPHA(2) MACROGLOBULIN GENE [J].
HOCKE, GM ;
BARRY, D ;
FEY, GH .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (05) :2282-2294
[9]   GROWTH-HORMONE AND PROLACTIN ARE PARACRINE GROWTH AND DIFFERENTIATION FACTORS IN THE HEMATOPOIETIC SYSTEM [J].
HOOGHE, R ;
DELHASE, M ;
VERGANI, P ;
MALUR, A ;
HOOGHEPETERS, EL .
IMMUNOLOGY TODAY, 1993, 14 (05) :212-214
[10]   THE GENOMIC STRUCTURE OF THE MURINE ICSBP GENE REVEALS THE PRESENCE OF THE GAMMA INTERFERON-RESPONSIVE ELEMENT, TO WHICH AN ISGF3-ALPHA SUBUNIT (OR SIMILAR) MOLECULE BINDS [J].
KANNO, Y ;
KOZAK, CA ;
SCHINDLER, C ;
DRIGGERS, PH ;
ENNIST, DL ;
GLEASON, SL ;
DARNELL, JE ;
OZATO, K .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (07) :3951-3963