The mechanisms responsible for the switch of prostate cancer from androgen-sensitive (AS) to androgen-insensitive (AI) form
are not well understood. Regulation of androgen receptor (AR), through which androgens control the expression of genes involved in
prostate cells proliferation, migration and death also involves its cross-talk with the other signaling pathways, transcription factors and
coregulatory proteins, such as β-catenin. With the aim to determine their possible contribution in triggering the switch from AS to AI
form, which occurs upon androgen deprivation therapy - AR, Akt and β-catenin expression were knocked-down with respective siRNAs.
Treatment of LNCaP prostate cells with siRNA for AR significantly reduced their proliferation (45-70%), expression of nuclear β-
catenin, cyclin-D1, cyclin-G1, c-Myc as well as activity of metalloproteinases (MMPs) -2,-7,-9 and cell migration. Surprisingly, after
longer (over 72 hrs) silencing of AR in LNCaP cells, elevated levels of p-Akt were detected and enhanced proliferation as well as expression
of nuclear β-catenin, cyclin-D1, c-Myc and activity of MMPs were observed. Such effects were not observed in either PC-3 or
DU145 AI cells. However, silencing of Akt and /or β-catenin in those as well as in LNCaP cells led to their decreased proliferation and
migration. Our findings suggest that in prostate cancer cells, either AR or Akt signaling prevails, depending on their initial androgen sensitivity
and its availability. In AI prostate cancer cells, Akt takes over the role of AR and more effectively contributes through the same
signaling molecule, β-catenin, to AI cancer progression.