Differential effects of dehydroepiandrosterone and testosterone in prostate and colon cancer cell apoptosis: the role of nerve growth factor (NGF) receptors.

Tumor growth is fostered by inhibition of cell death, which involves the receptiveness of tumor to growth factors and hormones. We have recently shown that testosterone exerts proapoptotic effects in prostate and colon cancer cells through a membrane-initiated mechanism. In addition, we have recently reported that dehydroepiandrosterone (DHEA) can control cell fate, activating nerve growth factor (NGF) receptors, namely tropomyosin-related kinase (Trk)A and p75 neurotrophin receptor, in primary neurons and in PC12 tumoral cells.

Serum- and glucocorticoid-dependent kinase-1-induced cell migration is dependent on vinculin and regulated by the membrane androgen receptor.

The serum- and glucocorticoid-dependent kinases 1-3 (SGK1-3) are downstream effectors of phosphatidylinositol 3-kinases, implicated in various cell responses including colon cancer tumorigenesis in mice. Here, we investigated the role of SGK1 in the regulation of cell motility. Using Caco-2 colon tumor and HEK293 embryonic kidney cells, we report that transfection with the constitutively active SGK1 mutant (SGK1-SD) significantly enhanced cell motility.

Membrane androgen receptor activation triggers down-regulation of PI-3K/Akt/NF-kappaB activity and induces apoptotic responses via Bad, FasL and caspase-3 in DU145 prostate cancer cells.

Background: Recently we have reported membrane androgen receptors-induced apoptotic regression of prostate cancer cells regulated by Rho/ROCK/actin signaling. In the present study we explored the specificity of these receptors and we analyzed downstream effectors controlling survival and apoptosis in hormone refractory DU145-prostate cancer cells stimulated with membrane androgen receptor-selective agonists.

Results: Using membrane impermeable conjugates of serum albumin covalently linked to testosterone, we show here down-regulation of the activity of pro-survival gene products, namely PI-3K/Akt and NF-kappaB, in DU145 cells.