The role of inhibitory transcription factor GCF on invasion and metastasis of gastrointestinal cancer and its genetic abnormality

点击翻译按钮获取中文摘要

1. The role of GCF in invasion and metastasis of gastrointestinal cancerThe expression vector of GCF gene was introduced gastric carcinoma cell lines and stable cell lines with GCF overexpression were established. In vitro growth was suppressed and tumorigenicity was reduced by GCF overexpression. However, both control cells and GCF-transfectants did not show metastatic ability. The levels of GCF in gastric carcinoma cell lines showed tendency to correlate with the expression and secretion of vascular endothelial growth factor (VEGF) which participates in tumor invasion and metastasis through angiogenesis. GCF did not affect the induction of VEGF by EGF in these cell lines.2.Genetic abnormality of GCFGenetic instability on GCF gene locus (D2S110, chromosome 2q14) was examined in gastric carcinomas and precancerous lesions by microsatellite analysis Replication error (RER (+) ) was detected in 17% of gastric carcinmas, many of which also showed RER in different loci such as D2S123 and D2S136. RER (+) of GCF gene locus was detected in 18% of gastric adenomas and none of intestinal metaplasia. This genetic instability may cause loss of GCF function, resulting in overexpression of several genes related to proliferation and progression.3. Molecular mechanism of invasion and metastasis of gastrointestinal cancerIt was found that cadherin-catenin system, beta1-integrin and 31kDa lactoside-binding lectin participate in invasion and metastasis of gastric carcinomas. HGF enhanced motility and scattering of gastric carcinoma cells, while HGF reduced the expression of E-and P-cadherin. The amplification and overexpression of cyclin E was associated with invasion and metastasis of gastric and colorectal carcinomas.