Regulation of amphiregulin mRNA by TGF-beta in the human lung adenocarcinoma cell line A549.
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.
Bennett
K L
KL
Bristol Myers Squibb, Seattle, Washington 98121.
Plowman
G D
GD
Buckley
S D
SD
Skonier
J
J
Purchio
A F
AF
D000230:Adenocarcinoma; D066258:Amphiregulin; D015152:Blotting, Northern; D002460:Cell Line; D066255:EGF Family of Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D006133:Growth Substances / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008175:Lung Neoplasms; D008970:Molecular Weight; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta