In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 998-998
Abstract:
Background: Survivin, identified member of the inhibitor apoptosis protein family, is expressed during development and in various human cancers. However, lts role of clinical relevance in cancers are sill debated. Purpose: We investigated the role of HGF induced activation of a transcription factor JunB, in the expression of survivin and uPA. Methods and Results: Genes induced by HGF were screened by using cDNA microarray technology in stomach cancer cell lines, NUGC3 and MKN28. Expression level of surviving and JunB was further confirmed by read time RT-RCR and western blot analysis. Roles of JunB and survivin in the levels of HGF induced up-regulation of uPA were measured by knock down of survivin with survivin siRNA and chromatic immuno- precipitation assay. The levels of JunB, survivin and uPA were up regulated in cells treated with HGF in a dose dependent manner. HGH-induced up regulations of JunB, surviving, and uPA were inhibited by the pretreatment with an MEK inhibitor, PD 098559. HGH-induced up-regulation of uPA were repressed by survivin knockdown. HGF enhanced the binding activity of JunB to the enhanced the binding activity of JunB to the survivin promoter in control cells, but not in the JunB-sh RNA cells. Transfection with survivin-sh RNA results in decrement of cell proliferation as determined with MTT assays. In an in vitro invasion assay, significantly fewer cells transfected with survivin sh-RNA than control cells were able to invade across a matrigel membrane barrier.Conclusion: Survivin might play an important role in the up-regulation of uPA induced by HGF via JunB and contribute to HGF-mediated tumor invasion and metastasis, which might be promising target for stomach cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 998. doi:10.1158/1538-7445.AM2011-998
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-998
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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