[Expressions and activities of Rho GTPases in hypoxia and its relationship with tumor angiogenesis].
OBJECTIVE
To study the expressions and activities of Rho GTPases in hypoxia and its relationship with tumor angiogenesis.


METHODS
Three tumor cell lines were used in this study: gastric cancer cell lines AGS, SGC7901 and hepatocellular carcinoma cell line HepG2. Expression level of Rac1 mRNA was detected by semi-quantitative RT-PCR. Activity of Rac1 was determined by pull-down assay and expression of HIF-1alpha, VEGF, p53 and PTEN protein was detected by Westernblot.


RESULTS
The expression level of Rac1 mRNA was significantly increased in hypoxia compared to normoxia. Pull-down assay showed that hypoxia-induced activity of Rac1 was elevated in a time-dependent manner and climaxed at 3 hours. The expressions of HIF-1alpha and VEGF protein were up-regulated, while those of PTEN and p53 protein were down-regulated.


CONCLUSIONS
These results indicate that hypoxia enhances Rac1 expression which might be involved in tumor angiogenesis by reacting with hypoxia-responsive genes.
Xue
Yan
Y
Insitute of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China.
Bi
Feng
F
Liu
Wen-chao
WC
Pan
Yang-lin
YL
Han
Zhe-yi
ZY
Liu
Na
N
Liu
Chang-jiang
CJ
Shen
Hui-qin
HQ
Zhang
Xue-yong
XY
D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D018197:Hepatoblastoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D051059:PTEN Phosphohydrolase; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins