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

Citation
M. Kondo 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(43), 2001, pp. 6258-6262
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
20
Issue
43
Year of publication
2001
Pages
6258 - 6262
Database
ISI
SICI code
0950-9232(20010927)20:43<6258:OOCTSG>2.0.ZU;2-A
Abstract
Recently we identified FUS1 as a candidate tumor suppressor gene (TSG) in t he 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 haplo-insufficien cy or low expression of Fus1 may play a role in lung tumorigenesis, we test ed the effect of exogenously induced overexpression of Fus1 protein and fou nd 60-80% inhibition of colony formation for non-small cell lung cancer lin es 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 suppr ess colony formation. Also, induced expression of Fus1 under the control of an Ecdysone regulated promoter decreased colony formation 75%, increased t he doubling time twofold, and arrested H1299 cells in G1. In conclusion, ou r 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 hu man cancers.