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• W2014163926 endingPage "375" @default.
• W2014163926 startingPage "367" @default.
• W2014163926 abstract "We previously showed that integrin αvβ3 overexpression and engagement by its ligand vitronectin increased adhesion, motility, and proliferation of human ovarian cancer cells. In search of differentially regulated genes involved in these tumor biological events, we previously identified the integrin-linked kinase (ILK) to be under control of αvβ3. In the present investigation we demonstrated significantly upregulated ILK protein as a function of αvβ3 in two ovarian cancer cell lines, OV-MZ-6 and OVCAR-3, and proved co-localization at the surface of αvβ3-overexpressing cells adherent to vitronectin. Increase of ILK protein was reflected by enhanced ILK promoter activity, an effect, which we further characterized with regard to transcriptional response elements involved. Abrogation of NF-κB/c-rel or p53 binding augmented ILK promoter activity and preserved induction by αvβ3. The AP1-mutant exhibited decreased promoter activity but was also still inducible by αvβ3. Disruption of the two DNA consensus motifs for Ets proteins led to divergent observations: mutation of the Ets motif at promoter position −462 bp did not significantly alter promoter activity but still allowed response to αvβ3. In contrast, disruption of the second Ets motif at position −85 bp did not only lead to slightly diminished promoter activity but also, in that case, abrogated ILK promoter induction by αvβ3. Subsequent co-transfection studies with ets-1 in the presence of the second Ets motif led to additional induction of ILK promoter activity. Taken together, these data suggest that ets-1 binding to the second Ets DNA motif strongly contributes to αvβ3-mediated ILK upregulation. By increasing ILK as an important integrin-proximal kinase, αvβ3 may promote its intracellular signaling and tumor biological processes arising thereof in favor of ovarian cancer metastasis. J. Cell. Physiol. 220: 367–375, 2009. © 2009 Wiley-Liss, Inc." @default.
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• W2014163926 date "2009-08-01" @default.
• W2014163926 modified "2023-10-11" @default.
• W2014163926 title "Integrin αvβ3 upregulates integrin-linked kinase expression in human ovarian cancer cells via enhancement of ILK gene transcription" @default.
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• W2014163926 doi "https://doi.org/10.1002/jcp.21774" @default.
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