Overexpression of Grb2-associated binder 2 in human lung cancer.

OBJECTIVE: Grb2-associated binder 2 (Gab2), a member of the family of Gab scaffolding adaptors, transmits and amplifies the signals from receptor tyrosine kinases. A recent study demonstrated that Gab2 was over-expressed in 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 analyzed the expression of Gab2 in 88 lung frozen tissue samples and 122 paraffin-embedded tissue specimens, using quantitative real-time-PCR, immunohistochemistry and western blot. RESULTS: 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 (12%) in normal lung tissues. The mRNA expression detected by quantitative real-time-PCR and protein expression detected by western blotting in different groups were consistent with the immunohistochemical results. 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 development.

Effect of chemokine receptors CCR7 on disseminated behavior of human T cell lymphoma: clinical and experimental study.

BACKGROUND: The expression of chemokine receptors CCR7 has been studied in relation to tumor dissemination and poor prognosis in a limited number of cancers. No such studies have been done on CCR7 expression in non-Hodgkin's lymphoma (T-NHL). Our aim in this paper is to investigate the association between CCR7 expression and progression and prognosis of T-NHL. METHODS: 1) Analysis of clinical data: The specimens were obtained from 41 patients with T-NHL and 19 patients with lymphoid hyperplasia. Their corresponding clinicopathologic data were also collected. The expression levels of CCR7, MMP-2, and MMP-9 were examined by immunohistochemical staining. 2) Human T-NHL cell lines Hut 78 (cutaneous T-cell lymphoma) and Jurkat (adult T-cell leukemia/lymphoma) were cultured. The invasiveness of the two cell lines were measured with a Transwell invasion assay, and then used to study the effects of chemokine receptors on T-NHL invasion and the underlying molecular mechanism. The transcript and expression of CCR7 were evaluated using RT-PCR and western blotting. RESULTS: 1) The higher CCR7 and MMP-9 expression ratios were significantly associated with multiple lesions and higher stage III/IV. Moreover, a positive correlation was observed between CCR7 and MMP-9 expression. 2) The Hut 78 cell line was more invasive than the Jurkat cells in the Transwell invasion assay. The transcript and expression levels of CCR7 were significantly higher in Hut78 than that of Jurkat cell line. The T-NHL cell lines were co-cultured with chemokine CCL21 which increased the invasiveness of T-NHL cell. The positive association between CCL21 concentration and invasiveness was found. 3) The stronger transcript and expression of PI(3)K, Akt and p- Akt were also observed in Hut78 than in Jurkat cell line. CONCLUSIONS: High CCR7 expression in T-NHL cells is significantly associated with lymphatic and distant dissemination as well as with tumor cell migration and invasion in vitro. Its underlying mechanism probably involves the PI(3)K/Akt signal pathway.

Estrogen promotes benzo[a]pyrene-induced lung carcinogenesis through oxidative stress damage and cytochrome c-mediated caspase-3 activation pathways in female mice.

Estrogen may contribute to the development of smoking-induced lung cancer in women. To test this hypothesis, an mouse model was used to investigate the effects of 17 beta-estradiol (E2) on benzo[a]pyrene (B[a]P)-induced lung carcinogenesis. We found that B[a]P could cause oxidative stress damage, upregulate mitochondrial cytochrome-c and caspase-3 expression, induce lung carcinogenesis in female mice, E2 promoted these effects of B[a]P while tamoxifen (TAM) inhibited this effects of E2. We conclude that E2 can promote the tumorigenic effects of B[a]P in female mice, and oxidative stress damage and activation of cytochrome-c-mediated caspase-3 pathway may be involved in this process.

Angiopoietin-3 overexpression in tobacco smoke-induced mouse lung tumors and its relation to vitamin E intervention.

Animal studies have shown that tobacco smoke can induce lung cancer in mice,and that the intake of Vitamin E (VE) has a protective effect against its risk. However, the mechanisms of action of VE remain unclear. In this study, DNA microarrays for gene expression profiles of the mouse genome were applied in order to screen for the upregulated genes associated with VE intervention in smoke-induced lung cancer. Real-time PCR was used to validate the screened upregulated angiopoietin-3 gene (Ang-3), and Western blotting was used to investigate the expression of the Ang-3 protein. Our results demonstrate that smoking and VE intervention involve 621 upregulated genes, including oncogenes, non-oncogenes with clear function and genes with unclear function. Of these, Ang-3 presented high expression in both the smoking and tumor groups. Real-time PCR and Western blotting further indicated that smoking could upregulate the expression of Ang-3; moreover, Ang-3 was overexpressed in lung cancer tissue. VE intervention decreased its expression to some extent. This illustrates that Ang-3 may play an important role in the carcinogenesis and development of smoke-induced lung cancer, and could also be a target in lung cancer treatment.