Abstract

BackgroundiASPP is a key inhibitor of tumour suppressor p53 and is found to be up-regulated in certain malignant conditions. The present study investigated the expression of iASPP in clinical lung cancer, a leading cancer type in the world, and the biological impact of this molecule on lung cancer cells.MethodsiASPP 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.ResultsWe 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.ConclusionsiASPP 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.

Highlights

  • IASPP is a key inhibitor of tumour suppressor p53 and is found to be up-regulated in certain malignant conditions

  • While ASPP1 and ASPP2 are down-regulated in a large percentage of tumours, iASPP has been found to be significantly higher in patients with acute leukaemia when compared with healthy donors or patients with leukaemia but with complete remission. iASPP has been found to be over-expressed in breast carcinomas [14,15,16,17,18,19]

  • Over-expression of the iASSP protein in human lung cancer tissues To determine the expression pattern of iASPP protein in human lung cancer, immunohistochemical analysis was performed on 49 pairs of tumour and normal tissues from patients pathologically verified for having lung carcinoma

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Summary

Introduction

IASPP is a key inhibitor of tumour suppressor p53 and is found to be up-regulated in certain malignant conditions. 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 iSAPP, Inhibitory Member of the ASPP (Apoptosisstimulating protein of p53) family is known as the Rela-associated inhibitor, RAI and NF-kappa-B-interacting protein-1, NKIP1. It is one of the conserved inhibitors of p53. There has been no reports on the expression of the ASPP family and their possible functions in lung cancer

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