Influence of dihydrotestosterone, epidermal growth factor, and basic fibroblast growth factor on the cell kinetics of the PC3, DU145, and LNCaP prostatic cancer cell lines: relationship with DNA ploidy level.
The cell kinetics (percentage of cells in the S+G2 phases of the cell cycle) and the DNA ploidy levels (nuclear DNA content) were determined in 108 samples each of the PC3, DU145, and LNCaP prostate cancer models. This was carried out by means of the digital cell image analysis of Feulgen-stained nuclei. Two to three hundred cell nuclei were analyzed for each of the 324 samples under study. The three cell lines were submitted to experimental conditions including the addition of dihydrotestosterone (DHT), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), either alone or in combination, to the culture media. The results show that under the present culture conditions, the PC3 cell line was DHT-, EGF- and bFGF-insensitive. In contrast to what is generally reported in the literature, the DU145 cell line was DHT- and EGF-sensitive under the present culture conditions, but bFGF-insensitive. The LNCaP cell line was DHT-sensitive, but EGF- and bFGF-insensitive. While mainly tetraploid, the three cell lines nevertheless exhibited a significant level of heterogeneity in their nuclear DNA content distributions. Indeed, the proportions of non-tetraploid (diploid, hyperdiploid, triploid, hypertriploid, hypertetraploid, polymorphic) DNA histograms were 14% in the PC3, 16% in the DU145, and 29% in the LNCaP cell lines. These results suggest that the DNA ploidy level would not influence the hormone sensitivity level in the cell lines since they had significantly distinct hormone sensitivity profiles while remaining mainly tetraploid.
D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D011003:Ploidies; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D013196:Dihydrotestosterone; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor