GENETIC CHANGES ASSOCIATED WITH THE ACQUISITION OF ANDROGEN-INDEPENDENT GROWTH, TUMORIGENICITY AND METASTATIC POTENTIAL IN A PROSTATE-CANCER MODEL

Genetic changes underlying the progression of human prostate cancer ar e incompletely understood. Recently, an experimental model system that resembles human prostate cancer progression was developed based on th e serial passage of an androgen-responsive, non-tumorigenic LNCaP pros tate cancer cell line into athymic castrated mice. Six different subli nes, derived after one, two or three rounds of in vivo passage, sequen tially acquired androgen independence and tumorigenicity as well as me tastatic capacity. Here, we used comparative genomic hybridization (CG H) and locus-specific fluorescence in situ hybridization (FISH) analys is to search for genetic changes that may underlie the phenotypic prog ression events in this model system. Six genetic aberrations were seen by CGH in the parental LNCaP cell line. The derivative sublines share d virtually all these changes, indicating a common clonal origin, but also contained 3-7 additional genetic changes. Gain of the 13q12-913 c hromosomal region as well as losses of 4, 6q24-qter, 20p and 21q were associated with androgen independence and tumorigenicity with addition al changes correlating with metastasis. In conclusion, an accumulation of genetic changes correlates with tumour progression in this experim ental in vivo model of prostate cancer progression. It is possible tha t the specific chromosomal aberrations involved in this model system m ay provide clues to the location of genes involved in human prostate c ancer progression and metastasis.