Using racially diverse PCa cell lines (MDA-PCa-2b, 22Rv1, PC3, and DU145) we examined the effects of glucocorticoids on the expression of two stress oncoproteins associated with PCa therapy resistance, Clusterin (CLU) and Lens Epithelium-Derived Growth Factor p75 (LEDGF/p75).
Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy.
LEDGF/p75 is overexpressed in PCa and other cancers, and promotes resistance to chemotherapy-induced cell death via the transactivation of survival proteins.
Our study identifies CYGB and other genes as stress genes potentially regulated by LEDGF/p75 in PCa cells, and provides a rationale for investigating their role in PCa and in promoting resistance to chemotherapy- and oxidative stress-induced cell death.
In conclusion, the malignancy of PCa seems to be accompanied by increased TrkA and TrkB signaling (with a reduction of p75 NGFR expression) and CEP-701 could be used to reduce the metastasis formation in advanced PCa.
Considering that TrkA receptor is related with proliferation and p75 with apoptosis, we suggest that our findings may explain, in part, the effect of GnRH analogs on prostate cancer growth.