NDF/heregulin-induced cell cycle changes and apoptosis in breast tumour cells: role of PI3 kinase and p38 MAP kinase pathways

被引：87

作者：

Daly, JM ^{[1
]}

Olayioye, MA ^{[1
]}

Wong, AML ^{[1
]}

Neve, R ^{[1
]}

Lane, HA ^{[1
]}

Maurer, FG ^{[1
]}

Hynes, NE ^{[1
]}

机构：

[1] Friedrich Miescher Inst, CH-4002 Basel, Switzerland

来源：

ONCOGENE | 1999年 / 18卷 / 23期

关键词：

apoptosis; cell cycle; ErbB receptors; PKB; c-Src kinase;

D O I：

10.1038/sj.onc.1202700

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neu differentiation factor (NDF)/heregulin activates ErbB2 via heterodimerization with the NDF receptors ErbB3 and ErbB4. Cells which express normal levels of these receptors are often growth stimulated by NDF, whereas SKBR3, and other ErbB2-overexpressing breast tumour cells are growth inhibited. We demonstrate here that in SKBR3 cells, NDF induces G1 progression but also causes a G2 delay from day 1 and apoptosis from days 2-3. G1 progression was associated with ErbB2 transactivation of ErbB3 and subsequent stimulation of the phosphatidylinositol 3-kinase (PI3K) whereas apoptosis was dependent on p38 MAPK. Inhibition of ERK1/ERK2 had no effect on cell cycle progression or apoptosis. Activation of ErbB3 and PI3K was also seen with betacellulin (BTC) but not epidermal growth factor (EGF) and. correlated with the growth effects of these ligands. All three ligands induced shortterm activation of p38 MAPK in a c-Src-dependent manner. However, only NDF caused a second, c-Src-independent increase in p38 MAPK activity which was required for apoptosis.

引用

页码：3440 / 3451

页数：12

共 65 条

[1] PD-098059 IS A SPECIFIC INHIBITOR OF THE ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE KINASE IN-VITRO AND IN-VIVO [J].