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.