Expression of Src and FAK in Hepatocellular Carcinoma and the Effect of Src Inhibitors on Hepatocellular Carcinoma In Vitro
| العنوان: | Expression of Src and FAK in Hepatocellular Carcinoma and the Effect of Src Inhibitors on Hepatocellular Carcinoma In Vitro |
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| المؤلفون: | Guo-Liang Yu, Grace M. Lau, Irwin H. Gelman, Alan Gutowski, David G. Hangauer, Jane W. S. Fang, Gillian M.G. Lau |
| المصدر: | Digestive Diseases and Sciences. 54:1465-1474 |
| بيانات النشر: | Springer Science and Business Media LLC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Physiology, Proto-Oncogene Proteins pp60(c-src), Dasatinib, In Vitro Techniques, Focal adhesion, Proliferating Cell Nuclear Antigen, Internal medicine, medicine, Humans, Aged, Cell Proliferation, biology, Cell growth, Liver Neoplasms, Gastroenterology, Middle Aged, medicine.disease, Immunohistochemistry, digestive system diseases, Proliferating cell nuclear antigen, Thiazoles, Pyrimidines, Endocrinology, Liver, Focal Adhesion Protein-Tyrosine Kinases, Hepatocellular carcinoma, Cancer cell, Disease Progression, biology.protein, Cancer research, Female, medicine.drug, Proto-oncogene tyrosine-protein kinase Src |
| الوصف: | The expressions of c-Src and focal adhesion kinase (FAK) were studied in 65 Chinese patients with hepatocellular carcinoma (HCC) by immunohistochemistry using rabbit monoclonal antibodies. Expressions of total Src, an active form of Src, and FAK were found in 44/65 (67.7%), 36/45 (55.4%), and 33/56 (58.9%) HCC cases, respectively. There was a good correlation between the expression of total Src, active form of Src, and FAK in these HCC cases (P < 0.001). Expression of Src was not correlated to any clinical parameters, cancer cell phenotypic markers, and pathologic features apart from a positive correlation with alpha-fetoprotein (P < 0.01). The expression of FAK was correlated with earlier onset and the expression of Ki-67 but not proliferating cell nuclear antigen (PCNA) in these HCC cases. Four liver-cancer-derived cell lines (three derived from HCC and one from hepatoblastoma) were then tested with inhibitors against Src. A small molecule, KX2-391, designed to target the substrate binding pocket of Src, was found to have more broad-spectrum activity and better potency than Dasatinib, an adenosine triphosphate (ATP)-competitive inhibitor in vitro. Our data indicates that Src and FAK expression are both elevated and active in Chinese patients with HCC and that Src may play a key role in supporting HCC progression. Src antagonism with specific inhibitors may be an attractive treatment paradigm for patients with HCC. |
| تدمد: | 1573-2568 0163-2116 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77bde6e811aed5c493babed7c6da5083Test https://doi.org/10.1007/s10620-008-0519-0Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....77bde6e811aed5c493babed7c6da5083 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15732568 01632116 |
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