Down‐modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3‐L1 preadipocytes
- 7 November 2007
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 104 (1), 274-285
- https://doi.org/10.1002/jcb.21621
Abstract
The high incidence of obesity-related pathologies, led to the study of the mechanisms involved in preadipose cell proliferation and differentiation. Here, we demonstrate that modulation of erbB2, plays a fundamental role during proliferation and adipogenic induction of preadipocytes. Using 3T3-L1 cells as model, we demonstrate that EGF (10 nM, 5 min) in addition to stimulate receptor tyrosine phosphorylation of both erbB2 and EGFR, is able to induce the heterodimer erbB2-EGFR. We treated proliferating 3T3-L1 cells with two inhibitors, AG 825 (IC50 0.35 µM, 54 times more selective for erbB2 than for EGFR, IC50 19 µM), and AG 879 (IC50 of 1 µM for erbB2 versus 500 µM for EGFR). We found that both inhibited the proliferation on a dose-dependent basis, reaching a 30% maximal inhibition at 100 µM (P < 0.001) for AG825, and a 20% maximal inhibition at 10 µM (P < 0.001) for AG 879. These results involve erbB2 in 3T3-L1 proliferation. When studying the differentiation process, we found that the action of MIX–Dexa immediately activates MEK, JNK and p38 kinases. We observed that PD98059 and SP600125 (MEK–ERK and JNK inhibitors, respectively) added 1 h prior to the MIX–Dexa induction produced a decrease in erbB2 expression after 6 h, which is even greater than the one produced by the inducers, MIX–Dexa. This work supports erbB2 as a key factor in 3T3-L1 adipogenesis, acting mostly and not only during the proliferative phase but also during the differentiation through modulation of both its expression and activity. J. Cell. Biochem. 104: 274–285, 2008.Keywords
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