Identification of a novel NOTCH-4/INT-3 RNA species encoding an activated gene product in certain human tumor cell lines

Akira Imatani, Robert Callahan

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)

Abstract

Ectopic expression of the intracellular domain of NOTCH-4/INT-3 leads to tumorigenesis in the mouse mammary gland. This results from a gain-of-function mutation. To evaluate gain-of-function NOTCH-4/INT3 activity in human cancers we have surveyed human breast, lung, and colon carcinoma tissue culture cell lines for evidence of increased NOTCH-4/INT-3 RNA expression. High levels of a 1.8 Kb NOTCH-4/INT-3 RNA species are detected in normal human testis but not in other tissues where a 6.5 Kb species is prevalent. Transformed human cancer cell lines express the 1.8 Kb NOTCH-4/INT-3 RNA species. We show that this RNA species encodes a truncated form of the NOTCH-4/INT3 intracellular domain (ICD). This novel NOTCH-4/INT-3 protein includes the CDC10 repeats and amino acid residues C-terminal to them, but is missing the CBF-1 binding region of the NOTCH-4/INT-3 ICD. This suggests that it has a different mode of action. Furthermore, we show that a transgene which expresses the 1.8 Kb NOTCH-4/INT-3 RNA species in the 'normal' human mammary epithelial cell line MCF-10A enables these cells to grow in soft agar.

Original languageEnglish
Pages (from-to)223-231
Number of pages9
JournalOncogene
Volume19
Issue number2
DOIs
Publication statusPublished - 2000 Jan 13
Externally publishedYes

Keywords

  • Activated gene product
  • Human
  • NOTCH-4/INT-3

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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