Abstract
BACKGROUND: Transferrin receptor (TfR) is expressed in most lung cancers and is an indicator of poor prognosis in certain groups of patients. In this study, we blocked cell surface TfR to inhibit lung adenocarcinoma (LAC) cell growth in vitro and investigated the associated molecular mechanisms to determine a potential therapeutic target in human LAC. METHODS: RNA interference and antibody blocking techniques were used to block the function of TfR in LAC cells, and cell proliferation assays were used to detect the results. Affymetrix microarray analysis was conducted using H1299 cells in which TfR was blocked with an antibody to investigate the molecular mechanisms involved. RESULTS: The cell proliferation assay demonstrated that H1299 cell proliferation was significantly inhibited after small interfering RNA knockdown or blocking of TfR. Mechanistic studies found that 100 genes were altered more than two-fold after TfR was blocked and that blocking TfR was accompanied by decreased expression of the oncogene KRAS. CONCLUSION: Our data provide evidence that blocking TfR could significantly inhibit LAC proliferation by targeting the oncogene KRAS; therefore, TfR may be a therapeutic target for LAC. In addition, our results suggest a new method for blocking the signal from the oncogene KRAS by targeting TfR in LAC.