The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis

Here we report the genetic characterization of immortalized prostate epithe lial cells before and after conversion to tumorigenicity using molecular cy togenetics and microarray technology. We were particularly interested to an alyze the consequences of acquired chromosomal aneuploidies with respect to modifications of gene expression profiles. Compared with nontumorigenic bu t immortalized prostate epithelium, prostate tumor cell lines showed high l evels of chromosomal rearrangements that led to gains of 1p, 5, 11q, 12p, 1 6q, and 20q and losses of 1pter, 11p, 17, 20p, 21, 22, and Y. Of 5700 uniqu e targets on a 6.5K cDNA microarray, similar to3% were subject to modificat ion in expression levels; these included GRO-1, -2, IAP-1,- 2, MMP-9, and c yclin D1, which showed increased expression, and TRAIL, BRCA1, and CTNNA, w hich showed decreased expression. Thirty % of expression changes occurred i n regions the genomic copy number of which remained balanced. Of the remain der, 42% of down-regulated and 51% of up-regulated genes mapped to regions present in decreased or increased genomic copy numbers, respectively. A rel ative gain or loss of a chromosome or chromosomal arm usually resulted in a statistically Significant increase or decrease, respectively, in the avera ge expression level of all of the genes on the chromosome. However, of thes e genes, very few (e.g., 5 of 101 genes on chromosome 11q), and in some ins tances only two genes (MMP-9 and PROCR on chromosome 20q), were overexpress ed by greater than or equal to1.7-fold when scored individually. Cluster an alysis by gene function suggests that prostate tumorigenesis in these cell line models involves alterations in gene expression that may favor invasion , prevent apoptosis, and promote growth.