Expression of seven gastric cancer-associated genes and its relevance for Wnt, NF-kappaB and Stat3 signaling.
The aim of the current study was to profile c-Myc, standard CD44 (CD44s), CD44v6, cyclin D1, survivin, MMP-7 and VEGF expression patterns in different gastric samples and to elucidate their relevance for Wnt, NF-kappaB and/or Stat3 activation using multiple experimental approaches. The results revealed that 87.1% (27/31) of gastric cancers and 8.7% (2/23) of noncancerous lesions (chronic gastritis and intestinal metaplasia) showed Wnt activation (Wnt(+)) that was closely related to the expression of the seven genes. Some Wnt(-) noncancerous lesions also expressed the above-mentioned genes, higher frequencies of survivin (7/8), VEGF (7/8), cyclin D1 (6/8) and c-Myc (5/8) but not CD44s (2/8), CD44v6 (3/8) and MMP-7 (2/8) being detected in the NF-kappaB(+) samples. Stat3 was activated in 37/54 gastric tissues, and in 3/4 VEGF, 4/6 c-Myc, 4/8 survivin, 2/4 MMP-7, 1/2 CD44v6, and 4/9 cyclin D1(+) but Wnt(-)/NF-kappaB(-) samples. These findings showed a close correlation in GCs between Wnt, NF-kappaB and Stat3 signaling and expression of the seven genes, the importance of NF-kappaB and Stat3 activation in regulating c-Myc, survivin, cyclin D1 and VEGF in noncancerous lesions, and the potential coordinative effects of these three signalings on GC formation presumably by promoting the transcription of their common target genes.
Han
Jing-Chun
JC
Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, P. R. China.
Zhang
Kai-Li
KL
Chen
Xiao-Yan
XY
Jiang
Hai-Feng
HF
Kong
Qing-You
QY
Sun
Yuan
Y
Wu
Mo-Li
ML
Huang
Lei
L
Li
Hong
H
Liu
Jia
J
D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D004789:Enzyme Activation / Q000502:physiology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D051154:Wnt2 Protein / Q000378:metabolism*
D017931:DNA Primers; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D051154:Wnt2 Protein