Frequent loss of Brm expression in gastric cancer correlates with histologic features and differentiation state

Nobutake Yamamichi, Ken Ichi Inada, Masao Ichinose, Mitsue Yamamichi-Nishina, Taketoshi Mizutani, Hirotaka Watanabe, Kazuya Shiogama, Mitsuhiro Fujishiro, Takuya Okazaki, Naohisa Yahagi, Takeshi Haraguchi, Shuji Fujita, Yutaka Tsutsumi, Masao Omata, Hideo Iba

研究成果: Article

74 引用 (Scopus)

抄録

The mammalian SWI/SNF chromatin remodeling complex, an essential epigenetic regulator, contains either a single Brm or BRG1 molecule as its catalytic subunit. We observed frequent loss of Brm expression but not of BRG1 in human gastric cancer cell lines. Treatment with histone deacetylase inhibitor rescued Brm expression, indicating epigenetic regulation of this gene, and an RNA interference-based colony formation assay revealed antioncogenic properties of Brm. Brm immunostaining of 89 primary gastric cancers showed an obvious reduction in 60 cases (67%) and a severe decrease in 37 cases (42%). Loss of Brm is frequent in the major gastric cancer types (well- or moderately- differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma) and positively correlates with the undifferentiated state. Among the minor gastric cancer types, Brm expression persists in signet-ring cell carcinoma and mucinous adenocarcinoma, but a marked decrease is observed in papillary adenocarcinoma. Intestinal metaplasia never shows decreased expression, indicating that Brm is a valid marker of gastric oncogenesis. In contrast, BRG1 is retained in most cases; a concomitant loss of BRG1 and Brm is rare in gastric cancer, contrary to other malignancies. We further show that Brm is required for villin expression, a definitive marker of intestinal metaplasia and differentiation. Via regulating such genes important for gut differentiation, Brm should play significant roles in determining the histologic features of gastric malignancy.

元の言語English
ページ(範囲)10727-10735
ページ数9
ジャーナルCancer Research
67
発行部数22
DOI
出版物ステータスPublished - 15-11-2007

Fingerprint

Stomach Neoplasms
Metaplasia
Epigenomics
Stomach
Adenocarcinoma
Signet Ring Cell Carcinoma
Papillary Adenocarcinoma
Mucinous Adenocarcinoma
Histone Deacetylase Inhibitors
Chromatin Assembly and Disassembly
RNA Interference
Genes
Catalytic Domain
Neoplasms
Carcinogenesis
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Yamamichi, N., Inada, K. I., Ichinose, M., Yamamichi-Nishina, M., Mizutani, T., Watanabe, H., ... Iba, H. (2007). Frequent loss of Brm expression in gastric cancer correlates with histologic features and differentiation state. Cancer Research, 67(22), 10727-10735. https://doi.org/10.1158/0008-5472.CAN-07-2601
Yamamichi, Nobutake ; Inada, Ken Ichi ; Ichinose, Masao ; Yamamichi-Nishina, Mitsue ; Mizutani, Taketoshi ; Watanabe, Hirotaka ; Shiogama, Kazuya ; Fujishiro, Mitsuhiro ; Okazaki, Takuya ; Yahagi, Naohisa ; Haraguchi, Takeshi ; Fujita, Shuji ; Tsutsumi, Yutaka ; Omata, Masao ; Iba, Hideo. / Frequent loss of Brm expression in gastric cancer correlates with histologic features and differentiation state. :: Cancer Research. 2007 ; 巻 67, 番号 22. pp. 10727-10735.
@article{03b019cb84b746728463beaf5a87d249,
title = "Frequent loss of Brm expression in gastric cancer correlates with histologic features and differentiation state",
abstract = "The mammalian SWI/SNF chromatin remodeling complex, an essential epigenetic regulator, contains either a single Brm or BRG1 molecule as its catalytic subunit. We observed frequent loss of Brm expression but not of BRG1 in human gastric cancer cell lines. Treatment with histone deacetylase inhibitor rescued Brm expression, indicating epigenetic regulation of this gene, and an RNA interference-based colony formation assay revealed antioncogenic properties of Brm. Brm immunostaining of 89 primary gastric cancers showed an obvious reduction in 60 cases (67{\%}) and a severe decrease in 37 cases (42{\%}). Loss of Brm is frequent in the major gastric cancer types (well- or moderately- differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma) and positively correlates with the undifferentiated state. Among the minor gastric cancer types, Brm expression persists in signet-ring cell carcinoma and mucinous adenocarcinoma, but a marked decrease is observed in papillary adenocarcinoma. Intestinal metaplasia never shows decreased expression, indicating that Brm is a valid marker of gastric oncogenesis. In contrast, BRG1 is retained in most cases; a concomitant loss of BRG1 and Brm is rare in gastric cancer, contrary to other malignancies. We further show that Brm is required for villin expression, a definitive marker of intestinal metaplasia and differentiation. Via regulating such genes important for gut differentiation, Brm should play significant roles in determining the histologic features of gastric malignancy.",
author = "Nobutake Yamamichi and Inada, {Ken Ichi} and Masao Ichinose and Mitsue Yamamichi-Nishina and Taketoshi Mizutani and Hirotaka Watanabe and Kazuya Shiogama and Mitsuhiro Fujishiro and Takuya Okazaki and Naohisa Yahagi and Takeshi Haraguchi and Shuji Fujita and Yutaka Tsutsumi and Masao Omata and Hideo Iba",
year = "2007",
month = "11",
day = "15",
doi = "10.1158/0008-5472.CAN-07-2601",
language = "English",
volume = "67",
pages = "10727--10735",
journal = "Cancer Research",
issn = "0008-5472",
number = "22",

}

Yamamichi, N, Inada, KI, Ichinose, M, Yamamichi-Nishina, M, Mizutani, T, Watanabe, H, Shiogama, K, Fujishiro, M, Okazaki, T, Yahagi, N, Haraguchi, T, Fujita, S, Tsutsumi, Y, Omata, M & Iba, H 2007, 'Frequent loss of Brm expression in gastric cancer correlates with histologic features and differentiation state', Cancer Research, 巻. 67, 番号 22, pp. 10727-10735. https://doi.org/10.1158/0008-5472.CAN-07-2601

Frequent loss of Brm expression in gastric cancer correlates with histologic features and differentiation state. / Yamamichi, Nobutake; Inada, Ken Ichi; Ichinose, Masao; Yamamichi-Nishina, Mitsue; Mizutani, Taketoshi; Watanabe, Hirotaka; Shiogama, Kazuya; Fujishiro, Mitsuhiro; Okazaki, Takuya; Yahagi, Naohisa; Haraguchi, Takeshi; Fujita, Shuji; Tsutsumi, Yutaka; Omata, Masao; Iba, Hideo.

:: Cancer Research, 巻 67, 番号 22, 15.11.2007, p. 10727-10735.

研究成果: Article

TY - JOUR

T1 - Frequent loss of Brm expression in gastric cancer correlates with histologic features and differentiation state

AU - Yamamichi, Nobutake

AU - Inada, Ken Ichi

AU - Ichinose, Masao

AU - Yamamichi-Nishina, Mitsue

AU - Mizutani, Taketoshi

AU - Watanabe, Hirotaka

AU - Shiogama, Kazuya

AU - Fujishiro, Mitsuhiro

AU - Okazaki, Takuya

AU - Yahagi, Naohisa

AU - Haraguchi, Takeshi

AU - Fujita, Shuji

AU - Tsutsumi, Yutaka

AU - Omata, Masao

AU - Iba, Hideo

PY - 2007/11/15

Y1 - 2007/11/15

N2 - The mammalian SWI/SNF chromatin remodeling complex, an essential epigenetic regulator, contains either a single Brm or BRG1 molecule as its catalytic subunit. We observed frequent loss of Brm expression but not of BRG1 in human gastric cancer cell lines. Treatment with histone deacetylase inhibitor rescued Brm expression, indicating epigenetic regulation of this gene, and an RNA interference-based colony formation assay revealed antioncogenic properties of Brm. Brm immunostaining of 89 primary gastric cancers showed an obvious reduction in 60 cases (67%) and a severe decrease in 37 cases (42%). Loss of Brm is frequent in the major gastric cancer types (well- or moderately- differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma) and positively correlates with the undifferentiated state. Among the minor gastric cancer types, Brm expression persists in signet-ring cell carcinoma and mucinous adenocarcinoma, but a marked decrease is observed in papillary adenocarcinoma. Intestinal metaplasia never shows decreased expression, indicating that Brm is a valid marker of gastric oncogenesis. In contrast, BRG1 is retained in most cases; a concomitant loss of BRG1 and Brm is rare in gastric cancer, contrary to other malignancies. We further show that Brm is required for villin expression, a definitive marker of intestinal metaplasia and differentiation. Via regulating such genes important for gut differentiation, Brm should play significant roles in determining the histologic features of gastric malignancy.

AB - The mammalian SWI/SNF chromatin remodeling complex, an essential epigenetic regulator, contains either a single Brm or BRG1 molecule as its catalytic subunit. We observed frequent loss of Brm expression but not of BRG1 in human gastric cancer cell lines. Treatment with histone deacetylase inhibitor rescued Brm expression, indicating epigenetic regulation of this gene, and an RNA interference-based colony formation assay revealed antioncogenic properties of Brm. Brm immunostaining of 89 primary gastric cancers showed an obvious reduction in 60 cases (67%) and a severe decrease in 37 cases (42%). Loss of Brm is frequent in the major gastric cancer types (well- or moderately- differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma) and positively correlates with the undifferentiated state. Among the minor gastric cancer types, Brm expression persists in signet-ring cell carcinoma and mucinous adenocarcinoma, but a marked decrease is observed in papillary adenocarcinoma. Intestinal metaplasia never shows decreased expression, indicating that Brm is a valid marker of gastric oncogenesis. In contrast, BRG1 is retained in most cases; a concomitant loss of BRG1 and Brm is rare in gastric cancer, contrary to other malignancies. We further show that Brm is required for villin expression, a definitive marker of intestinal metaplasia and differentiation. Via regulating such genes important for gut differentiation, Brm should play significant roles in determining the histologic features of gastric malignancy.

UR - http://www.scopus.com/inward/record.url?scp=36349006592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36349006592&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-07-2601

DO - 10.1158/0008-5472.CAN-07-2601

M3 - Article

C2 - 18006815

AN - SCOPUS:36349006592

VL - 67

SP - 10727

EP - 10735

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 22

ER -

Yamamichi N, Inada KI, Ichinose M, Yamamichi-Nishina M, Mizutani T, Watanabe H その他. Frequent loss of Brm expression in gastric cancer correlates with histologic features and differentiation state. Cancer Research. 2007 11 15;67(22):10727-10735. https://doi.org/10.1158/0008-5472.CAN-07-2601