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

Masashi Kondo, Lin Ji, Craig Kamibayashi, Yoshio Tomizawa, Dwight Randle, Yoshitaka Sekido, Jun Yokota, Vladimir Kashuba, Eugene Zabarovsky, Igor Kuzmin, Michael Lerman, Jack Roth, John D. Minna

Research output: Contribution to journalArticle

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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 haplo-insufficiency 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.

Original languageEnglish
Pages (from-to)6258-6262
Number of pages5
JournalOncogene
Volume20
Issue number43
DOIs
Publication statusPublished - 27-09-2001

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Tumor Suppressor Genes
Lung Neoplasms
Growth
Alleles
Ecdysone
Genetic Promoter Regions
Non-Small Cell Lung Carcinoma
Methylation
Neoplasms
Carcinogenesis
Proteins
Breast Neoplasms
Lung
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Kondo, Masashi ; Ji, Lin ; Kamibayashi, Craig ; Tomizawa, Yoshio ; Randle, Dwight ; Sekido, Yoshitaka ; Yokota, Jun ; Kashuba, Vladimir ; Zabarovsky, Eugene ; Kuzmin, Igor ; Lerman, Michael ; Roth, Jack ; Minna, John D. / 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. In: Oncogene. 2001 ; Vol. 20, No. 43. pp. 6258-6262.
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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 haplo-insufficiency 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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Kondo, M, Ji, L, Kamibayashi, C, Tomizawa, Y, Randle, D, Sekido, Y, Yokota, J, Kashuba, V, Zabarovsky, E, Kuzmin, I, Lerman, M, Roth, J & Minna, JD 2001, '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, vol. 20, no. 43, pp. 6258-6262. https://doi.org/10.1038/sj.onc.1204832

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. / Kondo, Masashi; Ji, Lin; Kamibayashi, Craig; Tomizawa, Yoshio; Randle, Dwight; Sekido, Yoshitaka; Yokota, Jun; Kashuba, Vladimir; Zabarovsky, Eugene; Kuzmin, Igor; Lerman, Michael; Roth, Jack; Minna, John D.

In: Oncogene, Vol. 20, No. 43, 27.09.2001, p. 6258-6262.

Research output: Contribution to journalArticle

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T1 - 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

AU - Kondo, Masashi

AU - Ji, Lin

AU - Kamibayashi, Craig

AU - Tomizawa, Yoshio

AU - Randle, Dwight

AU - Sekido, Yoshitaka

AU - Yokota, Jun

AU - Kashuba, Vladimir

AU - Zabarovsky, Eugene

AU - Kuzmin, Igor

AU - Lerman, Michael

AU - Roth, Jack

AU - Minna, John D.

PY - 2001/9/27

Y1 - 2001/9/27

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AB - 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 haplo-insufficiency 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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