Abstract
Anoikis is a form of programmed cell death induced in normal epithelial cells by detachment from the extracellular matrix. In epithelial cells of the intestine and other organs, activated ras induces resistance to anoikis, but the actual molecular effectors directly involved in the apoptotic machinery that execute or block anoikis have not yet been identified. Bak, a pro-apoptotic member of the Bcl-2 family, is downregulated in a high proportion of colorectal tumours. In addition, Bak is an important regulator of apoptosis in normal intestinal epithelial cells. Here, we show that activated ras induces the downregulation of Bak in rat and human intestinal epithelial cells. This ras-induced downregulation of Bak expression could be suppressed by an inhibitor of phosphatidylinositol (PI) 3-kinase, an enzyme already implicated in ras-induced resistance to anoikis. Ectopic expression of Bak in ras-transformed rat intestinal epithelial IEC-18 cells inhibited ras-induced resistance to anoikis and significantly reduced their tumorigenicity. We conclude, therefore, that the ability of ras to downregulate Bak, and the consequent resistance to anoikis, are essential components of the transforming capacity of this oncogene in intestinal epithelial cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1331-1334 |
| Number of pages | 4 |
| Journal | Current Biology |
| Volume | 8 |
| Issue number | 24 |
| State | Published - Dec 3 1998 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
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Downregulation of the pro-apoptotic protein Bak is required for the ras-induced transformation of intestinal epithelial cells. / Rosen, Kirill; Rak, Janusz; Jin, Jing; Kerbel, Robert S.; Newman, Michael J.; Filmus, Jorge.
In: Current Biology, Vol. 8, No. 24, 03.12.1998, p. 1331-1334.Research output: Contribution to journal › Article
TY - JOUR
T1 - Downregulation of the pro-apoptotic protein Bak is required for the ras-induced transformation of intestinal epithelial cells
AU - Rosen, Kirill
AU - Rak, Janusz
AU - Jin, Jing
AU - Kerbel, Robert S.
AU - Newman, Michael J.
AU - Filmus, Jorge
PY - 1998/12/3
Y1 - 1998/12/3
N2 - Anoikis is a form of programmed cell death induced in normal epithelial cells by detachment from the extracellular matrix. In epithelial cells of the intestine and other organs, activated ras induces resistance to anoikis, but the actual molecular effectors directly involved in the apoptotic machinery that execute or block anoikis have not yet been identified. Bak, a pro-apoptotic member of the Bcl-2 family, is downregulated in a high proportion of colorectal tumours. In addition, Bak is an important regulator of apoptosis in normal intestinal epithelial cells. Here, we show that activated ras induces the downregulation of Bak in rat and human intestinal epithelial cells. This ras-induced downregulation of Bak expression could be suppressed by an inhibitor of phosphatidylinositol (PI) 3-kinase, an enzyme already implicated in ras-induced resistance to anoikis. Ectopic expression of Bak in ras-transformed rat intestinal epithelial IEC-18 cells inhibited ras-induced resistance to anoikis and significantly reduced their tumorigenicity. We conclude, therefore, that the ability of ras to downregulate Bak, and the consequent resistance to anoikis, are essential components of the transforming capacity of this oncogene in intestinal epithelial cells.
AB - Anoikis is a form of programmed cell death induced in normal epithelial cells by detachment from the extracellular matrix. In epithelial cells of the intestine and other organs, activated ras induces resistance to anoikis, but the actual molecular effectors directly involved in the apoptotic machinery that execute or block anoikis have not yet been identified. Bak, a pro-apoptotic member of the Bcl-2 family, is downregulated in a high proportion of colorectal tumours. In addition, Bak is an important regulator of apoptosis in normal intestinal epithelial cells. Here, we show that activated ras induces the downregulation of Bak in rat and human intestinal epithelial cells. This ras-induced downregulation of Bak expression could be suppressed by an inhibitor of phosphatidylinositol (PI) 3-kinase, an enzyme already implicated in ras-induced resistance to anoikis. Ectopic expression of Bak in ras-transformed rat intestinal epithelial IEC-18 cells inhibited ras-induced resistance to anoikis and significantly reduced their tumorigenicity. We conclude, therefore, that the ability of ras to downregulate Bak, and the consequent resistance to anoikis, are essential components of the transforming capacity of this oncogene in intestinal epithelial cells.
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M3 - Article
VL - 8
SP - 1331
EP - 1334
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 24
ER -