iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway

iASPP protein levels in lung cancer tissues were evaluated using an immunohistochemical method. In vitro, iASPP gene expression was suppressed with a lentvirus-mediated shRNA method and the biological impact after knocking down iASSP on lung cancer cell lines was investigated in connection with the p53 expression status.We showed here that the expression of iASPP was significantly higher in lung cancer tissues compared with the adjacent normal tissues. iASPP shRNA treatment resulted in a down-regulation of iASPP in lung cancer cells. There was a subsequent reduction of cell proliferation of the two lung tumour cell lines A459 and 95D both of which had wild-type p53 expression. In contrast, reduction of iASPP in H1229 cells, a cell with little p53 expression, had no impact on its growth rate.iASPP regulates the proliferation and motility of lung cancer cells. This effect is intimately associated with the p53 pathway. Together with the pattern of the over-expression in clinical lung cancers, it is concluded that iASPP plays an pivotal role in the progression of lung cancer and is a potential target for lung cancer therapy.The tumour suppressor protein p53 is a transcription factor that responds to oncogenic stress such as DNA damage, oncogene activtaion, γ-irradiation and certain chemotherapeutic drugs that may result in apoptosis and cell-cycle arrest [1,2]. In over half of all of human cancers, p53 has been shown to be either lost or mutated. In those tumours in which the p53gene is intact, the regulation of the p53 pathway may be defect [3,4]. The type of response following p53 activation depends upon a number of factors. Importantly, oncogenic transformation can cause a switch in the cell's response to p53 activation from growth arrest to programmed cell death. As a result, tumour cells are more likely to undergo apoptosis following p53 activation than the corresponding normal cells, making the p53 pathway an excellent target for therapeutic intervention [5-8].iSA