Abstract
We report that artemin, a member of the glial cell line-derived neurotrophic factor family of ligands, is oncogenic for human mammary carcinoma. Artemin is expressed in numerous human mammary carcinoma cell lines. Forced expression of artemin in mammary carcinoma cells results in increased anchorage-independent growth, increased colony formation in soft agar and in three-dimensional Matrigel, and also promotes a scattered cell phenotype with enhanced migration and invasion. Moreover, forced expression of artemin increases tumor size in xenograft models and leads to highly proliferative, poorly differentiated and invasive tumors. Expression data in Oncomine indicate that high artemin expression is significantly associated with residual disease after chemotherapy, metastasis, relapse and death. Artemin protein is detectable in 65% of mammary carcinoma and its expression correlates to decreased overall survival in the cohort of patients. Depletion of endogenous artemin with small interfering RNA, or antibody inhibition of artemin, decreases the oncogenicity and invasiveness of mammary carcinoma cells. Artemin is therefore oncogenic for human mammary carcinoma, and targeted therapeutic approaches to inhibit artemin function in mammary carcinoma warrant consideration.
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Accession codes
Abbreviations
- BrdU:
-
bromodeoxyuridine
- EGFP:
-
enhanced green fluorescent protein
- ER:
-
estrogen receptor
- GDNF:
-
glial –cell line-derived neurotrophic factor
- GFL:
-
GDNF family ligand
- GFRα:
-
GDNF family receptor α
- PR:
-
progesterone receptor
- RT:
-
reverse transcription
- siRNA:
-
small interfering RNA
- TUNEL:
-
terminal doxynucleotidyl transferase-mediated dUTP nick end labeling
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Acknowledgements
We thank Alan Beedle for critical reading of the manuscript. This work was funded by the Breast Cancer Research Trust (NZ), the Foundation for Research, Science and Technology of New Zealand, the Hundred-Talent Scheme of Chinese Academy of Sciences, the National Natural Science Foundation of China (2007CB914801 & 2007CB914503) and the National Basic Research Program of China (30571030).
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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)
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Kang, J., Perry, J., Pandey, V. et al. Artemin is oncogenic for human mammary carcinoma cells. Oncogene 28, 2034–2045 (2009). https://doi.org/10.1038/onc.2009.66
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DOI: https://doi.org/10.1038/onc.2009.66
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