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RhoB is frequently downregulated in non‐small‐cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line
Author(s) -
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
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22328
Subject(s) - rhob , cancer research , biology , loss of heterozygosity , lung cancer , microbiology and biotechnology , pathology , gene , medicine , genetics , rhoa , signal transduction , allele
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, NCI‐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 RhoB 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 RhoB 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. © 2006 Wiley‐Liss, Inc.