Notch1-induced transformation of RKE-1 cells requires up-regulation of cyclin D1

Mark Stahl, Changhui Ge, Shaolin Shi, Richard G. Pestell, Pamela Stanley

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

RKE-1 cells induced to overexpress activated Notch 1 (RKE-ER-N ic) exhibit increased cyclin D1 transcripts and become transformed. However, the oncogenic pathway of Notch1-induced transformation is not known. Here, we use mutational analysis to functionally identify the sole region of the cyclin D1 promoter that responds to activated Notch1. The same region responds to activated Notch4 as well as to physiologic Notch ligand-induced Notch receptor signaling. The cyclin D1 gene was subsequently found to be a physiologic target of Notch signaling in Pofut1-/- mouse embryos defective in canonical Notch signaling and in embryos with an inactivating mutation in Notch1. To determine if Notch1-induced cyclin D1 expression in RKE-ER-Nic cells plays a direct role in transformation, cyclin D1 up-regulation was inhibited using a cyclin D1 antisense cDNA. We report here that transformation of RKE-ER-Nic cells is dependent on increased expression of cyclin D1 protein, which represents a new mechanism of Notch1-induced transformation.

Original languageEnglish (US)
Pages (from-to)7562-7570
Number of pages9
JournalCancer Research
Volume66
Issue number15
DOIs
StatePublished - Aug 1 2006

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Cyclin D1
Up-Regulation
Embryonic Structures
bcl-1 Genes
Notch Receptors
Complementary DNA
Ligands
Mutation
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Notch1-induced transformation of RKE-1 cells requires up-regulation of cyclin D1. / Stahl, Mark; Ge, Changhui; Shi, Shaolin; Pestell, Richard G.; Stanley, Pamela.

In: Cancer Research, Vol. 66, No. 15, 01.08.2006, p. 7562-7570.

Research output: Contribution to journalArticle

Stahl, Mark ; Ge, Changhui ; Shi, Shaolin ; Pestell, Richard G. ; Stanley, Pamela. / Notch1-induced transformation of RKE-1 cells requires up-regulation of cyclin D1. In: Cancer Research. 2006 ; Vol. 66, No. 15. pp. 7562-7570.
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