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Expression of concern: Characterization of a novel epigenetically‐silenced, growth‐suppressive gene, ADAMTS9 , and its association with lymph node metastases in nasopharyngeal carcinoma
Author(s) -
Lung Hong Lok,
Lo Paulisally Hau Yi,
Xie Dan,
Apte Suneel S.,
Cheung Arthur Kwok Leung,
Cheng Yue,
Law Evan Wai Lok,
Chua Daniel,
Zeng YiXin,
Tsao Sai Wah,
Stanbridge Eric J.,
Lung Maria Li
Publication year - 2008
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.23528
Subject(s) - biology , nasopharyngeal carcinoma , cancer research , tumor suppressor gene , lymph node , cell culture , pathology , microbiology and biotechnology , gene , carcinogenesis , immunology , medicine , genetics , radiation therapy
By using a functional complementation approach, suppression of tumorigenicity was observed after transfer of intact or truncated copies of chromosome 3 into a nasopharyngeal carcinoma (NPC) HONE1 cell line. The extra exogenous chromosome 3 in the microcell hybrids (MCHs) significantly extended the lag period of tumor formation, which may be associated with loss or inactivation of wild type alleles from the normal donor chromosome 3. Representative tumors, which grew in nude mice were reconstituted into culture and expanded as tumor segregants (TSs). In our study, a disintegrin‐like and metalloprotease with thrombospondin type 1 motif 9 (ADAMTS9 ), a gene mapping to 3p14.2, was identified to be critically associated with tumor suppression in NPC. Gene expression analysis showed that ADAMTS9 was either not expressed or was downregulated in HONE1 cells, TSs and NPC cell lines. The mechanism of ADAMTS9 gene inactivation in the NPC cell lines and tissues was attributed to promoter hypermethylation. Using a tissue microarray and immunohistochemical staining, 31 of 66 (47%) of the NPC cases showed downregulated or absence of ADAMTS9 expression. ADAMTS9 expression was downregulated or lost in 17 of 23 (73.9%) lymph node metastatic NPC specimens, which was significantly higher than in 14 of 43 (32.6%) primary tumors. After transfection of the ADAMTS9 gene into 7 NPC cell lines, a dramatic reduction of colony forming ability was observed. These findings support ADAMTS9 as a putative tumor suppressor gene in vivo in NPC that is significantly associated with lymph node metastases. © 2008 Wiley‐Liss, Inc.