| Objective:Grb2-associated binder protein 2 (Gab2), a member of the family of Gab scaffolding adaptors, transmits and amplifies the signals from receptor tyrosine kinases. As a key member of the family of Gab scaffolding adaptors, Gab2 can recruit many signal members (such as p85,SHP2 and Crk), which contribute to the initiation of signaling pathways promoting cellular growth, survival, migration and proliferation. A recent study demonstrated that Gab2 was over-expressed in ovarian, gastric, acute myeloid leukemia(AML), breast cancers and metastatic melanomas, and Gab2 was an oncogenic protein. However, the roles of Gab2 in lung cancers are largely unknown.Method:In this study, to investigate whether Gab2 expression could be a characteristic of lung cancers, we obtained all the specimens from Tianjin Medical University Tumor Hospital (from March to May 2010). Formalin-fixed, paraffin-embedded tumor tissues from 122 patients (25 normal lung tissues,40 squamous cell carcinomas,37 adenocarcinomas,20 other types of lung cancers) were sectioned (4μm thick). We also obtained 88 lung frozen tissue samples at the same time, using quantitative real-time-PCR, immunohistochemistry and western blot. RNA interference (RNAi) was used to explore the role of Gab2 protein silencing in A549 lung cancer cell lines.Results:1. We found that the positive expression rate of Gab2 in the tumor tissues, as detected by immunohistochemistry,62.5% in squamous cell cancers,51.35% in adenocarcinomas, and 75% in other types of lung cancers, was significantly higher than that in normal lung tissues (P<005). but there is no statistical significance of Gab2 expression among 3 groups of lung tumor samples.2. We make a further study to assess the relationship between Gab2 expression and clinic pathological features. There are only 17 other types of lung cancer specimens, except 3 small cell carcinomas, so we mainly analyzed the relation between Gab2 expression and clinic pathological features of patients with lung adenocarcinomas and squamous cell carcinomas. We found that Gab2 expression was related to tumor size (P=0.0170) and UICC staging (P=0.0079) in lung adenocarcinomas and squamous cell carcinomas, respectively, but not to age, gender, histological grade, lymph node metastasis and depth of invasion.3.15 lung cancer tissues and their corresponding normal lung tissues were available for evaluation of Gab2 mRNA expression by quantitative real-time PCR. The result showed that up-regulation of Gab2 mRNA in 10 lung tumor samples compared to that in corresponding normal lung tissues, which were peripheral normal tissues from the same donor (t=2.632, P=0.020<0.05).4. We examined the expression of Gab2 protein in 38 lung tumor samples (16 lung squamous cell carcinomas,16 lung adenocarcinomas and 6 other types of lung cancers) and 20 normal lung samples by western blot analysis. Results showed that Gab2 protein expressions were significantly higher in lung tumor samples than that in normal lung tissues (P=0.0023), but there is no statistical significance of Gab2 expression among 3 groups of lung tumor samples.5. Small interference RNA (siRNA) expressed by RNAi plasmid expression vector can inhibit the expression of Gab2 protein in A549 lung cancer lines.Conclusion:Our data indicate that Gab2 is over-expressed in malignant lung tissues compared with that in normal lung tissues, and suggest that Gab2 expression may play a role in lung cancer developmen... |
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