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Selective activation of tumor growth-promoting Ca2+ channel MS4A12 in colon cancer by caudal type homeobox transcription factor CDX2
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Titel: |
Selective activation of tumor growth-promoting Ca2+ channel MS4A12 in colon cancer by caudal type homeobox transcription factor CDX2 |
In: | Molecular Cancer, 8, 2009, 1 |
veröffentlicht: |
Springer Science and Business Media LLC
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ISSN: |
1476-4598 |
DOI: | 10.1186/1476-4598-8-77 |
Zusammenfassung: | <jats:title>Abstract</jats:title> <jats:p>Colon cancer-associated MS4A12 is a novel colon-specific component of store-operated Ca<jats:sup>2+</jats:sup> (SOC) entry sensitizing cells for epidermal growth factor (EGF)-mediated effects on proliferation and chemotaxis. In the present study, we investigated regulation of the <jats:italic>MS4A12</jats:italic> promoter to understand the mechanisms responsible for strict transcriptional restriction of this gene to the colonic epithelial cell lineage. DNA-binding assays and luciferase reporter assays showed that <jats:italic>MS4A12</jats:italic> promoter activity is governed by a single CDX homeobox transcription factor binding element. RNA interference (RNAi)-mediated silencing of intestine-specific transcription factors CDX1 and CDX2 and chromatin immunoprecipitation (ChIP) in LoVo and SW48 colon cancer cells revealed that <jats:italic>MS4A12</jats:italic> transcript and protein expression is essentially dependent on the presence of endogenous CDX2. In summary, our findings provide a rationale for colon-specific expression of <jats:italic>MS4A12</jats:italic>. Moreover, this is the first report establishing CDX2 as transactivator of tumor growth-promoting gene expression in colon cancer, adding to untangle the complex and conflicting biological functions of CDX2 in colon cancer and supporting MS4A12 as important factor for normal colonic development as well as for the biology and treatment of colon cancer.</jats:p> |
Format: | E-Article |
Quelle: | Springer Science and Business Media LLC (CrossRef) |
Sprache: | Englisch |