Rac1, an intracellular signal transducer, regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac1 has been reported in several human cancers. However, the underlying mechanisms are not well understood.
In the present study, we evaluated the possibility of Rac1 as an appropriate molecular target for cancer gene therapy. The expression of Rac1 in 150 primary non-small cell lung cancer tissues (NSCLC) and 30 normal paraneoplastic lung tissues was determined by immunohistochemical staining,
and the correlation of Rac1 overexpression with clinicopathological factors was evaluated. Overexpression of Rac1 was detected in 94 of 150 lung cancer specimens, the incidence rate being higher than that in normal lung tissue specimens. In addition, overexpression of Rac1 was also associated
with poor differentiation, high TNM stage, and lymph node metastasis in NSCLC patients. Moreover, RNAi-mediated suppression of Rac1 expression reduced lamellipodia formation, migration and invasion potential of a lung cancer cell carcinoma cell line, 801D. Down-regulation of Rac1 expression
also reduced the expression of Pak1. NSC23766, an inhibitor of Rac1 activity, could also inhibit lung cancer cell migration, invasion and induce rearrangements of the actin cytoskeleton. Furthermore, the suppression of Rac1 expression also sensitized cells to antitumor drugs. These results
indicate that the overexpression of Rac1 is tightly associated with an aggressive phenotype of lung cancer cells. Therefore, we proposed that Rac1 could be a potential molecular target of gene therapy by RNAi-targeting in lung cancer cells.
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Document Type: Research Article
Department of Respiratory Disease, The 117th Hospital of PLA, Hang Zhou 310013, P.R. China
Department of Oncology Disease, The 117th Hospital of PLA, Hang Zhou 310013, P.R. China
Publication date: November 1, 2011
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The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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