Regulation of Amphiregulin mRNA by TGF-beta in the Human Lung Adenocarcinoma Cell Line A549

被引:18
作者
Bennett, Kelly L. [1 ]
Plowman, Gregory D. [1 ]
Buckley, Sharon D. [1 ]
Skonier, John [1 ]
Purchio, A. F. [1 ]
机构
[1] Bristol Myers Squibb, Seattle, WA 98121 USA
关键词
TCF-beta; AR; EGF; growth inhibition;
D O I
10.3109/08977199209046925
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Transforming growth factor beta is a strong growth inhibitor for many types of normal and transformed cells, although little is known on the mechanism of this anti-proliferative effect. The human lung adenocarcinoma cell line A549 is growth arrested by TGF-beta 1 and serves as a model for studying this effect. We describe that, concurrent with the inhibition of A549 cell growth, TGF-beta 1 treatment causes a dramatic reduction in the level of expression of the amphiregulin (AR) gene, a recently identified member of the EGF/TGF alpha family. Similar results were also observed with TGF-beta 2. Peak inhibition occurred at 24 hr of treatment and was reversible upon removal of TGF-beta 1. The level of AR protein secreted by A549 cells was also decreased by TGF-beta 1. In contrast, TGF-alpha mRNA was not detected in these cells regardless of TGF-beta 1 treatment. Another TGF-beta inhibited cell line, PC-3 (human prostatic adenocarcinoma) also exhibited a decrease in AR message levels following exposure to TGF-beta 1. The growth inhibitory effects of TGF-beta may in part be mediated by modulation of AR expression.
引用
收藏
页码:207 / 213
页数:8
相关论文
共 50 条
  • [1] ASSOIAN RK, 1983, J BIOL CHEM, V258, P7155
  • [2] ASSOIAN RK, 1984, CELL, V36, P35, DOI 10.1016/0092-8674(84)90071-0
  • [3] ASSOIAN RK, 1985, J BIOL CHEM, V260, P9613
  • [4] THE CELL BIOLOGY OF TRANSFORMING GROWTH-FACTOR-BETA
    BARNARD, JA
    LYONS, RM
    MOSES, HL
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1990, 1032 (01) : 79 - 87
  • [5] TGF-BETA INDUCES BIMODAL PROLIFERATION OF CONNECTIVE-TISSUE CELLS VIA COMPLEX CONTROL OF AN AUTOCRINE PDGF LOOP
    BATTEGAY, EJ
    RAINES, EW
    SEIFERT, RA
    BOWENPOPE, DF
    ROSS, R
    [J]. CELL, 1990, 63 (03) : 515 - 524
  • [6] SOURCE OF ANTI-MULLERIAN HORMONE SYNTHESIZED BY FETAL TESTIS - MULLERIAN-INHIBITING ACTIVITY OF FETAL BOVINE SERTOLI CELLS IN TISSUE-CULTURE
    BLANCHARD, MG
    JOSSO, N
    [J]. PEDIATRIC RESEARCH, 1974, 8 (12) : 968 - 971
  • [7] BRUNNER AM, 1989, J BIOL CHEM, V264, P13660
  • [8] A HEPARIN SULFATE-REGULATED HUMAN KERATINOCYTE AUTOCRINE FACTOR IS SIMILAR OR IDENTICAL TO AMPHIREGULIN
    COOK, PW
    MATTOX, PA
    KEEBLE, WW
    PITTELKOW, MR
    PLOWMAN, GD
    SHOYAB, M
    ADELMAN, JP
    SHIPLEY, GD
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (05) : 2547 - 2557
  • [9] A NEW TYPE OF TRANSFORMING GROWTH FACTOR-BETA, TGF-BETA-3
    DERYNCK, R
    LINDQUIST, PB
    LEE, A
    WEN, D
    TAMM, J
    GRAYCAR, JL
    RHEE, L
    MASON, AJ
    MILLER, DA
    COFFEY, RJ
    MOSES, HL
    CHEN, EY
    [J]. EMBO JOURNAL, 1988, 7 (12) : 3737 - 3743
  • [10] HUMAN TRANSFORMING GROWTH FACTOR-BETA COMPLEMENTARY-DNA SEQUENCE AND EXPRESSION IN NORMAL AND TRANSFORMED-CELLS
    DERYNCK, R
    JARRETT, JA
    CHEN, EY
    EATON, DH
    BELL, JR
    ASSOIAN, RK
    ROBERTS, AB
    SPORN, MB
    GOEDDEL, DV
    [J]. NATURE, 1985, 316 (6030) : 701 - 705