| dc.description.abstract | p53 is a well-studied tumor suppressor gene. In the past, many conventional methods were used to identify p53 function-associated genes. In order to identified unknown genes whose function were related with p53, colormetric cDNA microarray were used to study the genome-wide transcriptional expression pattern of genes, which are regulated by tumor suppressor gene p53 in human non small cell lung cancer cell line H1299. To chase the downstream genes of p53, the cell line H1299-p53V173L was used for experiments since it expresses wild-type p53 once the growth temperature was shifted from 37℃ to 32℃. Post temperature shift from 37℃ to 32℃, cells were harvested at the following time intervals: 0, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours. The derived cDNA were labeled and hybridized to microarray membranes containing 9600 cDNA dots. The signal density of these cDNA dots were acquired with image processing for statistic analysis. Through such process, totally 144 genes were identified as p53-upregulated or p53-downregulated, and were further sequence verified. The majority of these genes are related with signal transduction, cell cycle, metabolic regulation and DNA repair. Some genes found associated with p53 in the literature were successfully identified, for instance, PCNA, ku80, APEX etc. According to the data in this thesis, p53 might control many genes expression, even though when cells were not stimulated by X-ray or hypoxia. Among those genes, the most interesting one is the MHC (major compatibility complex) class I, which plays a major role in immune response. Different alleles of MHC class I was observed significantly and consistently induced by p53. This indicates that p53 may be involved in some immune pathway to target stressed or tumor cells for elimination. The association between p53 and immune system was all the time totally ignored. With cDNA microarray technology, this association is confirmed and is worth with further investigation. | en_US |