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

• Published in: Cancer research (Chicago, Ill.) Vol. 61; no. 22; pp. 8143 - 8149
• Main Authors: PHILLIPS, John L, HAYWARD, Simon W, LINEHAN, W. Marston, CUNHA, Gerald R, RIED, Thomas, YUZHUO WANG, VASSELLI, James, PAVLOVICH, Christian, PADILLA-NASH, Hesed, PEZULLO, John R, GHADIMI, B. Michael, GROSSFELD, Gary D, RIVERA, Alexandra
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.11.2001
• Subjects: Aneuploidy; Biological and medical sciences; BRCA1 gene; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - pathology; chromosome 1; chromosome 11; chromosome 12; chromosome 16; chromosome 17; chromosome 20; chromosome 21; chromosome 22; chromosome 5; CTNNA gene; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - genetics; Humans; Karyotyping; Male; Medical sciences; MMP-9 gene; Nephrology. Urinary tract diseases; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; PROCR gene; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; TRAIL gene; Translocation, Genetic; Tumor Cells, Cultured; Tumors of the urinary system; Urinary tract. Prostate gland; Chromosomal aberration; Human; Urinary system disease; Prostate disease; Copy number; Aneuploidy; Malignant tumor; Gene expression; Cell transformation; Carcinogenesis; In vitro; Malignant transformation; Established cell line; Cytogenetics; Male genital diseases; Prostate
• ISSN: 0008-5472

Here we report the genetic characterization of immortalized prostate epithelial cells before and after conversion to tumorigenicity using molecular cytogenetics and microarray technology. We were particularly interested to analyze the consequences of acquired chromosomal aneuploidies with respect to modifications of gene expression profiles. Compared with nontumorigenic but immortalized prostate epithelium, prostate tumor cell lines showed high levels of chromosomal rearrangements that led to gains of 1p, 5, 11q, 12p, 16q, and 20q and losses of 1pter, 11p, 17, 20p, 21, 22, and Y. Of 5700 unique targets on a 6.5K cDNA microarray, approximately 3% were subject to modification in expression levels; these included GRO-1, -2, IAP-1,- 2, MMP-9, and cyclin D1, which showed increased expression, and TRAIL, BRCA1, and CTNNA, which showed decreased expression. Thirty % of expression changes occurred in regions the genomic copy number of which remained balanced. Of the remainder, 42% of down-regulated and 51% of up-regulated genes mapped to regions present in decreased or increased genomic copy numbers, respectively. A relative gain or loss of a chromosome or chromosomal arm usually resulted in a statistically significant increase or decrease, respectively, in the average expression level of all of the genes on the chromosome. However, of these genes, very few (e.g., 5 of 101 genes on chromosome 11q), and in some instances only two genes (MMP-9 and PROCR on chromosome 20q), were overexpressed by > or =1.7-fold when scored individually. Cluster analysis 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.