Early gene responses associated with transforming growth factor-beta 1 growth inhibition and autoinduction in MCF-7 breast adenocarcinoma cells.
In the human breast carcinoma cell line (MCF-7), exogenous TGF-beta 1 induces a dose-dependent inhibition of cell proliferation. In a MCF-7 cell subline [MCF-7(-)], which has an undetectable level of type II TGF-beta receptor, exogenous TGF-beta 1 does not inhibit cell proliferation but is still able to induce its own message. In both cell lines, TGF-beta 1 stimulates expression of c-jun, whereas a rapid, transient and marked increase in c-fos mRNA is only observed in the MCF-7 cells sensitive to the growth inhibitory effect of TGF-beta 1. Depletion of protein kinase C abolishes the c-fos but not the c-jun response to TGF-beta 1. Our results suggest that growth inhibition and autoinduction by TGF-beta 1 are mediated by different signalling pathways. In addition, a PKC-dependent increase in c-fos expression seems to be associated with the growth inhibitory effect of TGF-beta 1.
Lafon
C
C
Laboratorie de Pharmacologie et Toxicologie Fondamentales, CNRS, Toulouse, France.
Mazars
P
P
Guerrin
M
M
Barboule
N
N
Charcosset
J Y
JY
Valette
A
A
D030201:Activin Receptors, Type I; D000230:Adenocarcinoma / Q000378:metabolism; D000345:Affinity Labels; D001943:Breast Neoplasms / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000494:pharmacology*
D000345:Affinity Labels; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I