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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2000-01-13

AUTHORS

Akira Imatani, Robert Callahan

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/INT-3 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/INT-3 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. More... »

PAGES

223-231

Journal

TITLE

Oncogene

ISSUE

2

VOLUME

19

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.onc.1203295

    DOI

    http://dx.doi.org/10.1038/sj.onc.1203295

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1053478064

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10645000


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