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Presence of distinct AP‐1 dimers in normal and transformed rat hepatocytes under basal conditions and after epidermal growth factor stimulation
Author(s) -
Nadori F,
Lardeux B,
Rahmani M,
Bringuier A,
DurandSchneider A,
Bernuau D
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510260614
Subject(s) - junb , epidermal growth factor , messenger rna , immediate early gene , biology , microbiology and biotechnology , stimulation , cell growth , dna synthesis , gene expression , chemistry , cell culture , gene , endocrinology , dna , biochemistry , genetics
Activation of the transcriptional regulator AP‐1, a dimeric complex formed of various combinations of Fos and Jun proteins, is a key step in the cellular response to mitogens. Because different dimers are believed to display different regulatory functions, we hypothesized that transformed cells that lack normal growth constraints might display AP‐1 dimers that are different from those of normal cells. We therefore compared in primary and transformed rat hepatocytes (1) the composition of AP‐1 dimers under basal conditions and (2) AP‐1 induction by epidermal growth factor (EGF). Under basal conditions, AP‐1 contained predominantly Jun homodimers in both cell types. However, whereas normal hepatocytes contained only JunD, both JunD and JunB were present in the AP‐1 complex of 7777 cells. EGF treatment triggered almost identical programs of fos and jun gene activation at the messenger RNA (mRNA) level in both cell types, with an early accumulation of c‐fos, c‐jun, and junB mRNAs, but no change in junD mRNA levels. In both cell types, c‐Fos and Fra‐1 proteins increased after EGF treatment, but differences in the induction of Jun proteins were noted, with an increase of c‐Jun in hepatocytes and an increase of JunB in 7777 cells. In both cell types, activation of AP‐1 DNA binding activity by EGF was accompanied by the recruitment of Fra‐1 into AP‐1, detected earlier in 7777 cells than in hepatocytes, and with the transient appearance of c‐Fos in 7777 cells only. Finally, EGF activated AP‐1‐dependent transcription in 7777 cells but not in hepatocytes. These data indicate important differences in the functional activity of AP‐1 in transformed hepatocytes.