Abstract
Elevated expression of the integrin-linked kinase (ILK) has been observed in a variety of cancers and has been further correlated with poor clinical outcome. Here, we show that mammary epithelial disruption of ILK results in a profound block in mammary tumor induction. Consistent with these observations, inhibition of ILK function in ErbB2-expressing cells with small molecule inhibitor or RNA interference resulted in profound block in their in vitro invasive properties due to the induction of apoptotic cell death. The rare ILK-deficient tumors that eventually arose overcame this block in tumor induction by an upregulation of ErB3 phosphorylation. These observations provide direct evidence that ILK has a critical role in the initiation phase of ErbB2 tumor induction.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3374-3385 |
| Number of pages | 12 |
| Journal | Oncogene |
| Volume | 29 |
| Issue number | 23 |
| DOIs | |
| State | Published - Jun 10 2010 |
| Externally published | Yes |
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Keywords
- ErbB2
- Integrin-linked kinase
- Mammary tumorigenesis
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression : Implications for human breast cancer. / Pontier, S. M.; Huck, L.; White, D. E.; Rayment, J.; Sanguin-Gendreau, V.; Hennessy, B.; Zuo, D.; St-Arnaud, R.; Mills, Gordon; Dedhar, S.; Marshall, C. J.; Muller, W. J.
In: Oncogene, Vol. 29, No. 23, 10.06.2010, p. 3374-3385.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression
T2 - Implications for human breast cancer
AU - Pontier, S. M.
AU - Huck, L.
AU - White, D. E.
AU - Rayment, J.
AU - Sanguin-Gendreau, V.
AU - Hennessy, B.
AU - Zuo, D.
AU - St-Arnaud, R.
AU - Mills, Gordon
AU - Dedhar, S.
AU - Marshall, C. J.
AU - Muller, W. J.
PY - 2010/6/10
Y1 - 2010/6/10
N2 - Elevated expression of the integrin-linked kinase (ILK) has been observed in a variety of cancers and has been further correlated with poor clinical outcome. Here, we show that mammary epithelial disruption of ILK results in a profound block in mammary tumor induction. Consistent with these observations, inhibition of ILK function in ErbB2-expressing cells with small molecule inhibitor or RNA interference resulted in profound block in their in vitro invasive properties due to the induction of apoptotic cell death. The rare ILK-deficient tumors that eventually arose overcame this block in tumor induction by an upregulation of ErB3 phosphorylation. These observations provide direct evidence that ILK has a critical role in the initiation phase of ErbB2 tumor induction.
AB - Elevated expression of the integrin-linked kinase (ILK) has been observed in a variety of cancers and has been further correlated with poor clinical outcome. Here, we show that mammary epithelial disruption of ILK results in a profound block in mammary tumor induction. Consistent with these observations, inhibition of ILK function in ErbB2-expressing cells with small molecule inhibitor or RNA interference resulted in profound block in their in vitro invasive properties due to the induction of apoptotic cell death. The rare ILK-deficient tumors that eventually arose overcame this block in tumor induction by an upregulation of ErB3 phosphorylation. These observations provide direct evidence that ILK has a critical role in the initiation phase of ErbB2 tumor induction.
KW - ErbB2
KW - Integrin-linked kinase
KW - Mammary tumorigenesis
UR - http://www.scopus.com/inward/record.url?scp=77953477155&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953477155&partnerID=8YFLogxK
U2 - 10.1038/onc.2010.86
DO - 10.1038/onc.2010.86
M3 - Article
C2 - 20305688
AN - SCOPUS:77953477155
VL - 29
SP - 3374
EP - 3385
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 23
ER -