title: Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression.
abstract: 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.
authors: Cancer Genomics Project, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors: Yu
authors: Y
authors: Nakamura
authors: Toshiro
authors: T
authors: Migita
authors: Fumie
authors: F
authors: Hosoda
authors: Naoko
authors: N
authors: Okada
authors: Masahiro
authors: M
authors: Gotoh
authors: Yasuhito
authors: Y
authors: Arai
authors: Michiyo
authors: M
authors: Fukushima
authors: Misao
authors: M
authors: Ohki
authors: Satoshi
authors: S
authors: Miyata
authors: Kengo
authors: K
authors: Takeuchi
authors: Issei
authors: I
authors: Imoto
authors: Hitoshi
authors: H
authors: Katai
authors: Toshiharu
authors: T
authors: Yamaguchi
authors: Johji
authors: J
authors: Inazawa
authors: Setsuo
authors: S
authors: Hirohashi
authors: Yuichi
authors: Y
authors: Ishikawa
authors: Tatsuhiro
authors: T
authors: Shibata
mesh_terms: D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D022202:Chromosomes, Artificial, Bacterial; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D020868:Gene Silencing; D015894:Genome, Human; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D007834:Lasers; D008297:Male; D051379:Mice; D042282:Microdissection; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: C436492:KLF12 protein, human; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering