Abstract
Recently we identified FUS1 as a candidate tumor suppressor gene (TSG) in the 120 kb 3p21.3 critical region contained in nested lung and breast cancer homozygous deletions. Mutation of FUS1 is infrequent in lung cancers which we have confirmed in 40 other primary lung cancers. In addition, we found no evidence for FUS1 promoter region methylation. Because haploinsufficiency or low expression of Fus1 may play a role in lung tumorigenesis, we tested the effect of exogenously induced overexpression of Fus1 protein and found 60–80% inhibition of colony formation for non-small cell lung cancer lines NCI-H1299 (showing allele loss for FUS1) and NCI-H322 (containing only a mutated FUS1 allele) in vitro. By contrast, a similar level of expression of a tumor-acquired mutant form of FUS1 protein did not significantly suppress colony formation. Also, induced expression of Fus1 under the control of an Ecdysone regulated promoter decreased colony formation 75%, increased the doubling time twofold, and arrested H1299 cells in G1. In conclusion, our data are consistent with the hypothesis that FUS1 may function as a 3p21.3 TSG, warranting further studies of its function in the pathogenesis of human cancers.
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Abbreviations
- TSG:
-
tumor suppressor gene
- SCLC:
-
small cell lung cancer
- NSCLC:
-
non-small cell lung cancer
- LOH:
-
loss of heterozygosity
- SSCP:
-
single strand conformation polymorphism analysis
- FACS:
-
fluorescence activated cell sorter
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Acknowledgements
This work was supported by NCI grants CA71618 and Lung Cancer SPORE P50 CA70907, and the G Harold and Leila Y Mathers Charitable Foundation. V Kashuba and E Zabarovsky were funded by grants from the Swedish Cancer Society, Karolinska Institute and the Royal Swedish Academy of Science.
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Kondo, M., Ji, L., Kamibayashi, C. et al. Overexpression of candidate tumor suppressor gene FUS1 isolated from the 3p21.3 homozygous deletion region leads to G1 arrest and growth inhibition of lung cancer cells. Oncogene 20, 6258–6262 (2001). https://doi.org/10.1038/sj.onc.1204832
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DOI: https://doi.org/10.1038/sj.onc.1204832
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