Matriptase Activation and Shedding with HAI-1 Induced by Steroid Sex Hormones in Human Prostate Cancer Cells, but Not in Breast Cancer Cells

The study investigated the regulation of matriptase activation by steroid sex hormones in prostate and breast cancer cells. It found that 17beta-estradiol did not affect matriptase activation in breast cancer cells due to their high constitutive levels of activated matriptase. In contrast, very low levels of activated matriptase were detected in hormone-starved prostate cancer (LNCaP) cells, but robust activation occurred within 6 hours of exposure to 5alpha-dihydrotestosterone (DHT). This activation was followed by shedding of activated matriptase complexed with HAI-1 into the culture media, significantly reducing cellular levels of both proteins. The process was inhibited by the androgen antagonist bicalutamide, RNA transcription inhibitor actinomycin D, and protein synthesis inhibitor cycloheximide, indicating that androgen-induced matriptase activation in LNCaP cells required androgen receptor involvement, transcription, and protein synthesis.