RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line

Naohito Sato, Takayuki Fukui, Tetsuo Taniguchi, Toshihiko Yokoyama, Masashi Kondo, Tetsuro Nagasaka, Yasuhiro Goto, Wentao Gao, Yuichi Ueda, Kohei Yokoi, John D. Minna, Hirotaka Osada, Yutaka Kondo, Yoshitaka Sekido

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Abstract

Identification of a homozygous deletion in cancer cells provides strong evidence for the location of a tumor suppressor gene (TSG). We analyzed the 2p24 homozygous deletion of a non-small-cell lung cancer (NSCLC) cell line, NCT-H2882, and found that the deletion size was 3.7 Mbp. Since RhoB, which has been suggested to be a candidate TSG, was located in this region, we analyzed RhoB for alterations in NSCLC. Although we found no mutations in 48 cell lines including 20 NSCLCs, a loss of heterozygosity (LOH) analysis in 128 primary NSCLCs showed that 25 of 62 informative samples had LOH at the RhoB locus. Northern blot analysis of 28 cell lines (including 15 NSCLCs) indicated that RhoB expression was downregulated in 27. We analyzed KhoB expression in 112 primary NSCLCs with immunohistochemistry and found no or a weak RhoB expression in 33 (42%) of 78 adenocarcinomas, whereas we found it in 29 (94%) of 31 squamous cell carcinomas. No or a weak expression of RhoB was more frequently observed in poorly- or moderately-differentiated adenocarcinomas than in well-differentiated ones (p = 0.0014). Furthermore, no or a weak expression of RhoK indicated a tendency to poor patient prognosis. Although hypermethylation was not found at the promoter region, the RhoB expression in NSCLC cell lines was induced by histone deacetylase inhibition, suggesting that RhoB downregulation may be due to histone modification. The present study demonstrates that RhoB expression is frequently downregulated in NSCLCs by multiple mechanisms, suggesting that RhoB is a candidate TSG for NSCLC.

Original languageEnglish
Pages (from-to)543-551
Number of pages9
JournalInternational Journal of Cancer
Volume120
Issue number3
DOIs
Publication statusPublished - 01-02-2007

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Non-Small Cell Lung Carcinoma
Lung Neoplasms
Down-Regulation
Tumor Suppressor Genes
Cell Line
Loss of Heterozygosity
Adenocarcinoma
Histone Code
Histone Deacetylases
Genetic Promoter Regions
Northern Blotting
Squamous Cell Carcinoma
Immunohistochemistry
Mutation
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Sato, Naohito ; Fukui, Takayuki ; Taniguchi, Tetsuo ; Yokoyama, Toshihiko ; Kondo, Masashi ; Nagasaka, Tetsuro ; Goto, Yasuhiro ; Gao, Wentao ; Ueda, Yuichi ; Yokoi, Kohei ; Minna, John D. ; Osada, Hirotaka ; Kondo, Yutaka ; Sekido, Yoshitaka. / RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line. In: International Journal of Cancer. 2007 ; Vol. 120, No. 3. pp. 543-551.
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title = "RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line",
abstract = "Identification of a homozygous deletion in cancer cells provides strong evidence for the location of a tumor suppressor gene (TSG). We analyzed the 2p24 homozygous deletion of a non-small-cell lung cancer (NSCLC) cell line, NCT-H2882, and found that the deletion size was 3.7 Mbp. Since RhoB, which has been suggested to be a candidate TSG, was located in this region, we analyzed RhoB for alterations in NSCLC. Although we found no mutations in 48 cell lines including 20 NSCLCs, a loss of heterozygosity (LOH) analysis in 128 primary NSCLCs showed that 25 of 62 informative samples had LOH at the RhoB locus. Northern blot analysis of 28 cell lines (including 15 NSCLCs) indicated that RhoB expression was downregulated in 27. We analyzed KhoB expression in 112 primary NSCLCs with immunohistochemistry and found no or a weak RhoB expression in 33 (42{\%}) of 78 adenocarcinomas, whereas we found it in 29 (94{\%}) of 31 squamous cell carcinomas. No or a weak expression of RhoB was more frequently observed in poorly- or moderately-differentiated adenocarcinomas than in well-differentiated ones (p = 0.0014). Furthermore, no or a weak expression of RhoK indicated a tendency to poor patient prognosis. Although hypermethylation was not found at the promoter region, the RhoB expression in NSCLC cell lines was induced by histone deacetylase inhibition, suggesting that RhoB downregulation may be due to histone modification. The present study demonstrates that RhoB expression is frequently downregulated in NSCLCs by multiple mechanisms, suggesting that RhoB is a candidate TSG for NSCLC.",
author = "Naohito Sato and Takayuki Fukui and Tetsuo Taniguchi and Toshihiko Yokoyama and Masashi Kondo and Tetsuro Nagasaka and Yasuhiro Goto and Wentao Gao and Yuichi Ueda and Kohei Yokoi and Minna, {John D.} and Hirotaka Osada and Yutaka Kondo and Yoshitaka Sekido",
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Sato, N, Fukui, T, Taniguchi, T, Yokoyama, T, Kondo, M, Nagasaka, T, Goto, Y, Gao, W, Ueda, Y, Yokoi, K, Minna, JD, Osada, H, Kondo, Y & Sekido, Y 2007, 'RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line', International Journal of Cancer, vol. 120, no. 3, pp. 543-551. https://doi.org/10.1002/ijc.22328

RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line. / Sato, Naohito; Fukui, Takayuki; Taniguchi, Tetsuo; Yokoyama, Toshihiko; Kondo, Masashi; Nagasaka, Tetsuro; Goto, Yasuhiro; Gao, Wentao; Ueda, Yuichi; Yokoi, Kohei; Minna, John D.; Osada, Hirotaka; Kondo, Yutaka; Sekido, Yoshitaka.

In: International Journal of Cancer, Vol. 120, No. 3, 01.02.2007, p. 543-551.

Research output: Contribution to journalArticle

TY - JOUR

T1 - RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line

AU - Sato, Naohito

AU - Fukui, Takayuki

AU - Taniguchi, Tetsuo

AU - Yokoyama, Toshihiko

AU - Kondo, Masashi

AU - Nagasaka, Tetsuro

AU - Goto, Yasuhiro

AU - Gao, Wentao

AU - Ueda, Yuichi

AU - Yokoi, Kohei

AU - Minna, John D.

AU - Osada, Hirotaka

AU - Kondo, Yutaka

AU - Sekido, Yoshitaka

PY - 2007/2/1

Y1 - 2007/2/1

N2 - Identification of a homozygous deletion in cancer cells provides strong evidence for the location of a tumor suppressor gene (TSG). We analyzed the 2p24 homozygous deletion of a non-small-cell lung cancer (NSCLC) cell line, NCT-H2882, and found that the deletion size was 3.7 Mbp. Since RhoB, which has been suggested to be a candidate TSG, was located in this region, we analyzed RhoB for alterations in NSCLC. Although we found no mutations in 48 cell lines including 20 NSCLCs, a loss of heterozygosity (LOH) analysis in 128 primary NSCLCs showed that 25 of 62 informative samples had LOH at the RhoB locus. Northern blot analysis of 28 cell lines (including 15 NSCLCs) indicated that RhoB expression was downregulated in 27. We analyzed KhoB expression in 112 primary NSCLCs with immunohistochemistry and found no or a weak RhoB expression in 33 (42%) of 78 adenocarcinomas, whereas we found it in 29 (94%) of 31 squamous cell carcinomas. No or a weak expression of RhoB was more frequently observed in poorly- or moderately-differentiated adenocarcinomas than in well-differentiated ones (p = 0.0014). Furthermore, no or a weak expression of RhoK indicated a tendency to poor patient prognosis. Although hypermethylation was not found at the promoter region, the RhoB expression in NSCLC cell lines was induced by histone deacetylase inhibition, suggesting that RhoB downregulation may be due to histone modification. The present study demonstrates that RhoB expression is frequently downregulated in NSCLCs by multiple mechanisms, suggesting that RhoB is a candidate TSG for NSCLC.

AB - Identification of a homozygous deletion in cancer cells provides strong evidence for the location of a tumor suppressor gene (TSG). We analyzed the 2p24 homozygous deletion of a non-small-cell lung cancer (NSCLC) cell line, NCT-H2882, and found that the deletion size was 3.7 Mbp. Since RhoB, which has been suggested to be a candidate TSG, was located in this region, we analyzed RhoB for alterations in NSCLC. Although we found no mutations in 48 cell lines including 20 NSCLCs, a loss of heterozygosity (LOH) analysis in 128 primary NSCLCs showed that 25 of 62 informative samples had LOH at the RhoB locus. Northern blot analysis of 28 cell lines (including 15 NSCLCs) indicated that RhoB expression was downregulated in 27. We analyzed KhoB expression in 112 primary NSCLCs with immunohistochemistry and found no or a weak RhoB expression in 33 (42%) of 78 adenocarcinomas, whereas we found it in 29 (94%) of 31 squamous cell carcinomas. No or a weak expression of RhoB was more frequently observed in poorly- or moderately-differentiated adenocarcinomas than in well-differentiated ones (p = 0.0014). Furthermore, no or a weak expression of RhoK indicated a tendency to poor patient prognosis. Although hypermethylation was not found at the promoter region, the RhoB expression in NSCLC cell lines was induced by histone deacetylase inhibition, suggesting that RhoB downregulation may be due to histone modification. The present study demonstrates that RhoB expression is frequently downregulated in NSCLCs by multiple mechanisms, suggesting that RhoB is a candidate TSG for NSCLC.

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