Identification of genes involved in radiation-induced G1 arrest

The advent of microarray gene expression technology permits the simultaneous analysis of the levels of expression of thousands of genes and provides large dataset requiring multivariate analysis tools. Multiple genetic factors may modulate the occurrence and magnitude of the arrest in the G, phase of the cell cycle following exposure to ionizing radiation in human tumour cell lines. The ability to G, arrest after exposure to gamma rays and the global gene expression profile, evaluated by cDNA microarray technology, have been reported for the National Cancer Institute (NCI) 60 tumour cell lines panel. The sensitivity of the tumour cell lines to radiations represents an activity fingerprinting that can be correlated by partial least squares (PLS) to the transcriptional profiles of the same cell lines. VIP values obtained by the PLS method are able to detect transcripts relevant to the radiation-induced G, arrest. High VIP values were obtained for the basal levels of transcripts such as p21/Waf1/Cip1 and MDM2, that are well known for their roles in G, arrest after irradiation. Novel functional relationships suggested by high VIP values can be investigated experimentally. As an example, in the present study, we report that the transcript for the FLJ11046 protein is induced dose-dependently by gamma-irradiation in a cell line with mutated p53, but not in cell lines with wild-type p53. Moreover specific silencing of FLJ11046 transcript by RNA interference technology results in a block of cell growth.