Arg tyrosine kinase expression in human gastric adenocarcinoma is associated with vessel invasion.
ABSTRACT Gastric cancer is one of the prevalent cancer types in the Far East region. In order to discover new prognostic and diagnostic biomarkers for gastric cancer progression, we have used degenerated PCR primers designed to amplify all expressed protein tyrosine kinase molecules from human cancer tissues. In previous studies, we have shown the clinical significance of arg tyrosine kinases in a colorectal cancer progression model.
We further investigated the protein expression of arg tyrosine kinase by immunohistochemistry and analyzed the clinicopathological association with human cancers.
Specimens from 79 patients were examined and this demonstrated that the expression of arg kinase showed no statistically significant correlation with the patients' overall survival. However, higher levels of arg kinase immunoreactivity did show a statistically significant association with vessel invasion in gastric cancer tissues examined. This indicates a potential involvement of arg in gastric cancer invasion and progression.
- SourceAvailable from: Mohammad Reza Ataollahi[show abstract] [hide abstract]
ABSTRACT: There are some evidences on involvement of ABL2 in a number of cancers, especially ABL2 overexpression was observed in Raji, a Burkitt's lymphoma (BL) cell line. Therefore ABL2 overexpression may be involved in pathogenesis of Burkitt's lymphoma. The aim of this study was to evaluate ABL2 significance in BL. For this purpose 20 formaldehyde fixed paraffin embedded blocks – 16BL and 4 normal lymph nodes – were used. Sections were prepared from the paraffin blocks and treat with primary and then secondary antibodies. Two proteins, ABL2 (the test protein) and GAPDH (a control house keeping protein) were studied, ABL2 was labeled green and GAPDH red. After capturing the pictures using a CCD camera, the intensity of green and red colures were measured and ratio between green/red, that demonstrate changes in ABL2 expression, were calculated. The expression of ABL2 protein in BL and normal lymph node was considerably different and BL had higher expression of ABL2 protein compared to normal lymph nodes. The mean ratio of ABL2/GAPDH in Bl and normal lymph node was 0.68 and 0.65, respectively. Like other malignancies, finding about gene expression patterns in BL seems to be helpful in future board therapeutic guidelines. Then specific inhibitors of ABL2 would be considered as new chemotherapy agents in BL treatment.Islamic Republic of Iran. 01/2007; 18:215-220.
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ABSTRACT: Although c-Abl and Arg non-receptor tyrosine kinases are well known for driving leukemia development, their role in solid tumors has not been appreciated until recently. Accumulating evidence now indicates that c-Abl and/or Arg are activated in some solid tumor cell lines via unique mechanisms that do not involve gene mutation/translocation, and c-Abl/Arg activation promotes matrix degradation, invasion, proliferation, tumorigenesis, and/or metastasis, depending on the tumor type. However, some data suggest that c-Abl also may suppress invasion, proliferation, and tumorigenesis in certain cell contexts. Thus, c-Abl/Arg may serve as molecular switches that suppress proliferation and invasion in response to some stimuli (e.g., ephrins) or when inactive/regulated, or as promote invasion and proliferation in response to other signals (e.g., activated growth factor receptors, loss of inhibitor expression), which induce sustained activation. Clearly, more data are required to determine the extent and prevalence of c-Abl/Arg activation in primary tumors and during progression, and additional animal studies are needed to substantiate in vitro findings. Furthermore, c-Abl/Arg inhibitors have been used in numerous solid tumor clinical trials; however, none of these trials were restricted to patients whose tumors expressed highly activated c-Abl/Arg (targeted trial). Targeted trials are critical for determining whether c-Abl/Arg inhibitors can be effective treatment options for patients whose tumors are driven by c-Abl/Arg.Genes & cancer 05/2012; 3(5-6):414-25.
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ABSTRACT: Microarray gene expression profiling has been used to distinguish histological subtypes of renal cell carcinoma (RCC), and consequently to identify specific tumor markers. The analytical procedures currently in use find sets of genes whose average differential expression across the two categories differ significantly. In general each of the markers thus identified does not distinguish tumor from normal with 100% accuracy, although the group as a whole might be able to do so. For the purpose of developing a widely used economically viable diagnostic signature, however, large groups of genes are not likely to be useful. Here we use two different methods, one a support vector machine variant, and the other an exhaustive search, to reanalyze data previously generated in our Lab (Lenburg et al. 2003). We identify 158 genes, each having an expression level that is higher (lower) in every tumor sample than in any normal sample, and each having a minimum differential expression across the two categories at a significance of 0.01. The set is highly enriched in cancer related genes (p = 1.6 x 10⁻¹²), containing 43 genes previously associated with either RCC or other types of cancer. Many of the biomarkers appear to be associated with the central alterations known to be required for cancer transformation. These include the oncogenes JAZF1, AXL, ABL2; tumor suppressors RASD1, PTPRO, TFAP2A, CDKN1C; and genes involved in proteolysis or cell-adhesion such as WASF2, and PAPPA.Cancer informatics 02/2007; 3:65-92.