BACKGROUND: In Australia, 1 in 8 men are diagnosed with prostate cancer before the age of 75, and it remains the second highest cause of cancer death in men.While much work has been done in characterising genetic translocations in prostate cancer, there has been little investigation into the causative factors. Notably, androgens have been found to induce the formation of the TMPRSS2-ERG genetic fusion. Since oestrogen and insulin-like growth factor (IGF-1) have been found to affect androgen receptor signalling, it is plausible they may also affect the occurrence of translocations.
AIMS: This study aimed to identify pharmaceuticals, hormones and growth factors that affect the incidence of genetic translocation events in prostate cancer, as well as characterising differences between the effects of the androgens testosterone and dihydrotestosterone (DHT).
METHODS & RESULTS: Investigations were preformed on the LNCAP and LAPC4 prostate cancer cell lines after treatment. Polymerase chain reaction (PCR) and fluorescence in situ hybridisation (FISH) were then utilised to investigate the frequency of TMPRSS2-ERG formation. This investigation found that both DHT and testosterone significantly induced TMPRSS2-ERG formation in LAPC4 cells. However, only DHT was seen to significantly increase the incidence of TMPRSS2-ERG in the LNCAP cell line. Other hormones and growth factors such as oestrogen and IGF1 were seen to increase the rate of TMPRSS2-ERG formation but ultimately fell short of significance.