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The Expression Of Protien Kinase B, Inducible Factor-1α In Gastric Cancer And Their Relationship With Tumor Angiogenesis

Posted on:2008-01-20Degree:MasterType:Thesis
Country:ChinaCandidate:J D FuFull Text:PDF
GTID:2144360212993898Subject:Internal Medicine
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ObjectiveTo investigate the expression the gene of Akt1, Akt2, Akt3 and Hypoxia inducible factor la (HIF-1α) in gastric cancer. To investigate the expression of protien kinase B(PKB)and HIF-1α protien so that to analyze the relationship among Akt/HIF-1α pathway in human gastric carcinomas, and the relationship between Akt/HIF-1α pathway and vascellum-poietic so that we can found a new pass in diagnosis and treatment in gastric cancer MethodRT-PCR was used to detect the transcriptase of Akt1, Akt2, Akt3 and HIF-1α mRNA in 26 pairs of gastric cancer tissues and para-cancer tissues. The expression of pAkt and HIF-1αin 64 gastric carcinomas and 26 para-cancer tissues respectively were evaluated by immunohistochemistry, microvessel density(MVD) marker by CD34. Results(1) Akt1, Akt 2 and Akt3 mRNA were constitutively expressed in gastric specimens and their levels in cancerous tissues were not significantly different with those in para-cancer tissues (P >0.05). the expressions of HIF-1α mRNA in cancerous tissues were significant higher than para-cancer tissues(l.36±0.14v5'0.54±0.18,P < 0.05).(2) The positive expression rate pAkt in gastric cancer75% (48/ 64) was remarkably higher than that gastric by-cancer normal tissuesl5.4% (4/26), (x~2=26.936, P < 0.05 ) .In gastric cancer, the expression of pAkt was remarkably associated with TNM stage, invasive depth , lymph-node metastasis and distant invision, (P < 0.05).(3) The MVD of the HIF-1α positive expression group (26.52±4.11) was remarkablyhigher than that of the negative expression group (22.41±5.34) .(4) The positive expression rate HIF-1α in gastric cancer65.6% (42/64) was remarkably higher than that gastric by-cancer normal tissues 19.2% (5/26) ,(x~2 =15.950, P <0.05).In gastric cancer, the expression of HIF-1α was remarkably associated with TNM stage, invasive depth , lymph-node metastasis and distant invision,(P <0.05).(5) The MVD of the HIF-1α positive expression group(24.44±7.79)was remarkablyhigher than that of the negative expression group(19.37±5.2).(6) MVD was remarkably associated with TNM stage, invasive depth, lymph-nodemetastasis and distant invasion. (P <0.05)(7) In the case of gastric cancer, the MVD of pAkt and HIF-1α positively expressedgroup higher than pAkt and HIF-1α expressed negatively (t =3. 947,P < 0.05) .There was a positive correlation between expression of pAkt and HIF-1α,(Pearsonr =0.583, P <0.05) . Conclusions(1) Akt1, Akt 2 and Akt3 mRNA are not constitutively expressed in gastric cancer, but HIF-1α is overexpressed in gastric cancer.(2) The overexpression of PKB and HIF-1α in gastric cancer have a significant relationship with tumor angiogenesis(3) PKB, HIF-1α and MVD are significantly correlated with TNM stage, invasive depth and lymph-node metastasis of gastric cancer, their overexpression may lead to advanced invasion of gastric cancer and unfavorable prognosis.(4) PKB and HIF-1α may have played a corporative action in gastric cancer, their simultaneous expression may lead to tumor angiogenesis increasing greatly, cancer invading easily.(5) PKB and HIF-1α are distinctively overexpressed in gastric tissues, they have significant correlations with cell proliferation, apoptosis and metastasis of gastriccancer.
Keywords/Search Tags:protein kinase, phosphorylated, PKB/Akt, hypoxia inducible factor-1α, microvessel density(MVD), gastric cancer, Reverse transcription PCR, immunohistochemistry
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