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Krüppel‐like factor 12 plays a significant role in poorly differentiated gastric cancer progression
Author(s) -
Nakamura Yu,
Migita Toshiro,
Hosoda Fumie,
Okada Naoko,
Gotoh Masahiro,
Arai Yasuhito,
Fukushima Michiyo,
Ohki Misao,
Miyata Satoshi,
Takeuchi Kengo,
Imoto Issei,
Katai Hitoshi,
Yamaguchi Toshiharu,
Inazawa Johji,
Hirohashi Setsuo,
Ishikawa Yuichi,
Shibata Tatsuhiro
Publication year - 2009
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.24538
Subject(s) - gene knockdown , gene , biology , cancer , cancer research , locus (genetics) , oncogene , krüppel , microarray , complementary dna , microarray analysis techniques , microbiology and biotechnology , genetics , gene expression , cell cycle
Gastric cancer is the second common malignant neoplasia in Japan, and its poorly differentiated form is a deadly disease. To identify novel candidate oncogenes contributing to its genesis, we examined copy‐number alterations in 50 primary poorly differentiated gastric cancers using an array‐based comparative genomic hybridization (array‐CGH). Many genetic changes were identified, including a novel amplification of the 13q22 locus. Several genes are located in this locus, and selective knockdown of one for the Krüppel‐like factor 12 (KLF12) induced significant growth‐arrest in the HGC27 gastric cancer cell line. Microarray analysis also demonstrated that genes associated with cell proliferation were mostly changed by KLF12 knockdown. To explore the oncogenic function of KLF12, we introduced a full length of human KLF12 cDNA into NIH3T3 and AZ‐521 cell lines and found that overexpression significantly enhanced their invasive potential. In clinical samples, KLF12 mRNA in cancer tissue was increased in 11 of 28 cases (39%) when compared with normal gastric epithelium. Clinicopathological analysis further demonstrated a significant correlation between KLF12mRNA levels and tumor size ( p = 0.038). These data suggest that the KLF12 gene plays an important role in poorly differentiated gastric cancer progression and is a potential target of therapeutic measures. © 2009 UICC