当前位置： SCI文献检索 > CANCER RESEARCH期刊下所有文献 > Transforming growth factor beta induces apoptosis through repressing the phosphoinositide 3-kinase/AKT/survivin pathway in colon cancer cells.

Transforming growth factor beta induces apoptosis through repressing the phosphoinositide 3-kinase/AKT/survivin pathway in colon cancer cells.

Abstract：

:FET cells, derived from an early-stage colon carcinoma, are nontumorigenic in athymic mice. Stable transfection of a dominant-negative transforming growth factor beta (TGFbeta) type II receptor (DNRII) into FET cells that express autocrine TGFbeta shows loss of TGFbeta signaling and increased tumorigenicity in vivo indicating tumor suppressor activity of TGFbeta signaling in this model. The ability of tumorigenic cells to withstand growth factor and nutrient deprivation stress (GFDS) is widely regarded as a key attribute for tumor formation and progression. We hypothesized that increased tumorigenicity of FET/DNRII cells was due to loss of participation of autocrine TGFbeta in a "fail-safe" mechanism to generate cell death in response to this stress. Here, we document that loss of autocrine TGFbeta in FET/DNRII cells resulted in greater endogenous cell survival in response to GFDS due to activation of the phosphoinositide 3-kinase (PI3K)/Akt/survivin pathway. Treatment of FET DNRII cells with a PI3K inhibitor (LY294002) inhibited Akt phosphorylation and reduced survivin expression resulting in increased apoptosis in FET/DNRII cells. We also show that exogenous TGFbeta increased apoptosis in FET cells through repression of the PI3K/Akt/survivin pathway during GFDS. These results indicate that the PI3K/Akt/survivin pathway is blocked by TGFbeta signaling and that loss of autocrine TGFbeta leads to increased cell survival during GFDS through the novel linkage of TGFbeta-mediated repression of survivin expression. Inhibition of survivin function by dominant-negative approaches showed that this inhibitor of apoptosis family member is critical to cell survival in the FET/DNRII cells, thus indicating the importance of this target for TGFbeta-mediated apoptosis.

journal_name

Cancer Res

journal_title

Cancer research

authors

Wang J,Yang L,Yang J,Kuropatwinski K,Wang W,Liu XQ,Hauser J,Brattain MG

doi

10.1158/0008-5472.CAN-07-5348

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

3152-60

issue

eissn

0008-5472

issn

1538-7445

pii

68/9/3152

journal_volume

pub_type

杂志文章

在线工具

Transforming growth factor beta induces apoptosis through repressing the phosphoinositide 3-kinase/AKT/survivin pathway in colon cancer cells.