Abrogation of TGFβ signaling induces apoptosis through the modulation of MAP kinase pathways in breast cancer cells

Xiufen Lei, Junhua Yang, Robert W. Nichols, L. Z. Sun

Producción científica: Articlerevisión exhaustiva

18 Citas (Scopus)

Resumen

Transforming growth factor beta (TGFβ) can modulate the activity of various MAP kinases. However, how this pathway may mediate TGFβ-induced malignant phenotypes remains elusive. We investigated the role of autocrine TGFβ signaling through MAP kinases in the regulation of cell survival in breast carcinoma MCF-7 cells and untransformed human mammary epithelial cells (HMECs). Our results show that abrogation of autocrine TGFβ signaling with the expression of a dominant negative type II TGFβ receptor (DNRII) or the treatment with a TGFβ type I receptor inhibitor significantly increased apoptosis in MCF-7 cell, but not in HMEC. The expression of DNRII markedly decreased activated/phosphorylated Erk, whereas increased activated/phosphorylated p38 in MCF-7 cells. In contrast, there was no or little change of phosphorylated Erk and p38 in HMECs after the expression of DNRII. Inhibition of Erk activity in MCF-7 control cell induced apoptosis whereas restoration of Erk activity in MCF-7 DNRII cell reduced apoptosis. Similarly, inhibition of p38 activity also inhibited apoptosis in MCF-7 DNRII cell. Thus, autocrine TGFβ signaling can enhance the survival of MCF-7 cells by maintaining the level of active Erk high and the level of active p38 low. Furthermore, the survival properties of TGFβ pathway appear related to transformation supporting the notion that it may be a potential target for cancer therapy.

Idioma originalEnglish (US)
Páginas (desde-hasta)1687-1695
Número de páginas9
PublicaciónExperimental Cell Research
Volumen313
N.º8
DOI
EstadoPublished - may 1 2007

ASJC Scopus subject areas

  • Cell Biology

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