Expressions of IgG,Gab2 and PTEN in human glioma and their clinical significance / 实用医学杂志

Objective To investigate the expressions of IgG,Gab2 and PTEN in human gliomas and analyze their relationship with patient prognosis. Methods Immunohistochemistry was performed to detect the expressions of IgG,Gab2 and PTEN in 55 cases of gliomas and 20 cases of normal brain tissues. The mRNA expression of IgG in glioma tissues was detected by in situ hybridization. Results IgG protein and IgG mRNA were expressed in glioma tissues. IgG,Gab2,PTEN expression rate in normal brain tissues was significantly different to that in glioma-tissues(5.0%vs. 69.0%,5.0%vs. 52.7%,and 85.0%vs. 25.5%,P<0.05). Expression of IgG was positively related with expression of Gab2 in glioma(r = 0.3124,P < 0.05),IgG and PTEN expression were negatively related with each other(r=-0.422,P<0.05). Conclusions IgG and Gab2 are highly expressed in glioma. The expression of PTEN was downregulated in glioma. IgG,Gab2 and PTEN might be involved in the development of glioma.

Correlation between Gab2 expression in ovarian cancer and resistance to platinum drugs chemotherapy / 重庆医学

Objective To investigate the correlation between Gab2 expression and platinum drugs chemotherapy resistance by detecting the expression of Gab2 in ovarian cancer.Methods Immunohistochemical and Western blotting techniques were used to detect the expression of Gab2 in 107 specimens of serous ovarian tumor tissue and 12 specimens of normal ovarian tissues resected during bladder cancer radical operation in the department of gynaecology of our hospital from January 2011 to June 2015.The correlation between Gab2 expression with clinical stage and effect of combined chemotherapy based on platinum drugs was analyzed.Results The Gab2 expression level in ovarian cancer tissue was significantly higher than that in normal ovarian tissue,moreover had a relation with the FIGO clinical stage,the expression level of Gab2 increased with the increase of clinical stage,the difference was statistically significant (P<0.05);61 cases were sensitive to chemotherapy,46 cases were resistant to chemotherapy,the Gab2 expression level in the patients with chemotherapy resistance was significantly higher than that in the patients with chemotherapy sensitivity,the difference was statistically significant (P<0.05).Conclusion Gab2 may become one of effective indexes for predicting platinum drugs chemotherapy sensitivity.

GAB2 Amplification in Squamous Cell Lung Cancer of Non-Smokers

Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015. Clinical characteristics were reviewed, and DNA was extracted from fresh frozen lung cancer specimens. All of copy number alterations from ArrayCGH were validated using The Cancer Genome Atlas (TCGA) copy number variation (CNV) data of lung SCC. We examined the frequency of copy number changes according to the smoking status (non-smoker [n = 8] or smoker [n = 11]). We identified 16 significantly altered regions from ArrayCGH data, three gain and four loss regions overlapped with the TCGA lung squamous cell carcinoma (LUSC) patients. Within these overlapped significant regions, we detected 15 genes that have been reported in the Cancer Gene census. We also found that the proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smokers patients and vice versa in both ArrayCGH and TCGA data. Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers.

Expression and significance of Gab2 in colorectal cancer tissues / 中国免疫学杂志

Objective:To investigate the expression and significance of Gab 2 in colorectal cancer tissues .Methods:Immuno-histochemistry was used to detect the expression of Gab 2 in 78 cases of colorectal cancer tissues and 46 cases of the adjacent tissues and to analyze the association of Gab2 expression with the clinicopathologic features of colorectal cancer;The expression of Gab2 in samples from 10 cases of colorectal cancer tissues and matched adjacent nontumorous tissues was detected by Western blot .Results: The results of immunohistochemistry demonstrated that the Gab 2 protein positive expression rate in 78 cases of colorectal cancer was 53.85%;whereas was negative expression or weak in the adjacent tissues , showing a significant difference of comparison within this result (P0.05) .Western blot showed that the Gab2 protein expression of colorectal cancer cases was significantly higher than that of matched adjacent nontumorous tissues ( P<0.05 ).Conclusion: Gab2 was overexpressed in colorectal cancer .Gab2 maybe play an important role in carcinogenesis and progression of colorectal carcinoma .

Effects of Gab2 overexpression on proliferation and migration of human colorectal cancer cell line SW480 / 中国免疫学杂志

Objective:To investigate the effects of Gab2 overexpression on the proliferation and migration of human colorectal cancer cell line SW480.Methods: The experimental group (LV-Gab2-GFP group),colorectal cancer SW480 cells were transfected with recombinant lentivirus vector (LV-Gab2-GFP),the negative control group was transfected with negative control lentiviral vector ( LV-GFP) ,and the blank control group without any treatment.The mRNA and protein expression of Gab 2 in cells were identified by RT-PCR and Western blot respectively.Proliferation of the cells was detected by CCK-8 colorimeter and colony forming assay.Wound-healing assay was used to determine the cells migration .Results: RT-PCR and Western blot demonstrated that Gab 2 mRNA and protein expression significantly increased in LV-Gab2-GFP group compared with control groups;overexpression of Gab2 markedly enhanced human colorectal cancer SW 480 cells proliferation and migration compared with control groups .Conclusion:Overexpression of Gab2 accelerates human colorectal cancer SW 480 cells proliferation and migration.

Gab2 effects the invasion and metastasis of breast carcinoma through PI3 K/Akt/ARK5/MMP signal pathway / 中国药理学通报

Aim To investigate the molecular mecha-nism of Gab2 in the invasion and metastasis of breast cancer and provide a theoretical basis for clinical pre-vention of breast cancer invasion and metastasis. Methods The Gab2 , MMP-2 and MMP-9 expressions in 80 cases of breast cancer were detected by immuno-histochemistry . Western blot was used to detect the ex-pression of Gab2 protein in MDA-MB-231 cells and MCF-7 cells. The siRNA plasmid was used to transfect MDA-MB-231 cells. Western blot was used to detect the proteins expression of Gab2 , MMP-2 and MMP-9 . Transwell in vitro experiment was used to detect the in-vasion ability of each group transfected MDA-MB-231 cells, Western blot was used to analyze phosphorylation of Akt and ARK5 induced by epithelial growth factor ( EGF ) in transfected cells ( SiGab2/MDA-MB-231 and Scr/MDA-MB-231 ) . Results The expression of Gab2 protein in invasive ductal carcinoma was signifi-cantly higher than in normal breast tissue ( P<0. 01 ) . The expression of Gab2 was dramatically correlated with lymph node metastasis, ER expression, tumor his-tological grade, MMP-2 and MMP-9 (P<0. 05). The expression of Gab2 protein in MDA-MB-231 cells was higher than in MCF-7 cells. The expression of Gab2, MMP-2 and MMP-9 decreased in SiGab2/MDA-MB-231 cells and the invasion ability of SiGab2/MDA-MB-231 cells was significantly decreased ( P<0. 05 ) , and after 5 minutes’ stimulating by EGF, the phosphoryla-tion of Akt and ARK5 was significantly reduced. Con-clusion Gab2 can promote the invasion and metasta-sis of breast cancer by effecting the expression of MMP-2 and MMP-9 through PI3 K/ Akt /ARK5 signal path-way.

Gab2-Akt-ARK5 signaling pathway is associated with the invasion of glioma cells / 中国肿瘤临床

Objective:This study aimed to investigate the effect and significance of a binding protein-2 (Gab2)-Akt-ARK5 signaling pathway on the invasion of glioma cells. Methods:Immunohistochemical methods were used to detect the expressions of Gab2 and ARK5 in 45 cases of glioma tissue. siRNA plasmid was used to transfect LN-229 cells, and western blot was performed to analyze the protein expressions of Gab2 and ARK5. In vitro Matrigel invasion assay was conducted to detect variations in the invasiveness of transfected cells. Western blot was also conducted to analyze the protein phosphorylation of Akt and ARK5 in the cells transfected with Gab2 plasmid. Results:Immunohistochemical assay revealed that the expressions of ARK5 and Gab2 in glioma cells were positively correlated, and both expressions were higher in high-grade glioma (WHO gradeⅢ,Ⅳ) than in low-grade glioma (WHO gradeⅠ,Ⅱ). LN-229 cells transfected with ARK5 plasmid, Gab2 plasmid, ARK5 and Gab2 plasmid, and control plasmid were named siARK5/LN-229, siGab2/LN-229, siARK5 and siGab2/LN-229, and SCR/LN-229, respectively. After transfection was performed, the protein expressions of ARK5 and Gab2 were respectively decreased in siARK5/LN-229 and siGab2/LN-229. The protein expressions of ARK5 and Gab2 in siARK5 and siGab2/LN-229 were also respectively decreased. After ARK5 or Gab2 was downregulated, the number of glioma cells, which invaded and penetrated Matrigel, was decreased (P<0.01). The number of glioma cells also decreased significantly after ARK5 and Gab2 were downregulated. The phosphorylation of Akt and ARK5 in siGab2/LN-229 cells was decreased after these cells were stimulated by insulin-like growth factor-1. Conclusion:The silencing of ARK5 or Gab2 impaired glioma cell invasiveness. The decreased protein expression of Gab2 inhibited the phosphorylation of Akt and ARK5. These results suggested that the Gab2-Akt-ARK5 signaling pathway could be relevantly involved in glioma cell invasion.