Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression.
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.
Nakamura
Yu
Y
Cancer Genomics Project, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Migita
Toshiro
T
Hosoda
Fumie
F
Okada
Naoko
N
Gotoh
Masahiro
M
Arai
Yasuhito
Y
Fukushima
Michiyo
M
Ohki
Misao
M
Miyata
Satoshi
S
Takeuchi
Kengo
K
Imoto
Issei
I
Katai
Hitoshi
H
Yamaguchi
Toshiharu
T
Inazawa
Johji
J
Hirohashi
Setsuo
S
Ishikawa
Yuichi
Y
Shibata
Tatsuhiro
T
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*
C436492:KLF12 protein, human; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering