Development of an androgen-deprivation induced and androgen suppressed human prostate cancer cell line

Abstract

Background: Emergence of recurrent cells during androgen-deprivation therapy and intermittent androgen suppression therapy suggest that a subset of prostate cancer cells survive and proliferate in the androgen deprivation condition. Some of the recurrent cells that emerge during the androgen-deprivation therapy and intermittent androgen suppression therapy could be suppressed by replacement of androgen. In an attempt to recapitulate the clinical phenomenon, we developed an androgen-deprivation induced and androgen suppressed human prostate cancer cell line.

Methods: LNCS, an androgen-deprivation induced and androgen suppressed human prostate cancer cell line, was generated from an androgen-sensitive LNCaP cells cultured in PRMI-1640 media containing charcoal-stripped FBS for a prolong period for more than a year. The responsiveness to androgen in vitro and in vivo was examined. The characteristics of this subline including activation of signaling pathways were investigated.

Results: LNCS, an androgen-deprivation induced and androgen suppressed human prostate cancer cell line, was developed. LNCS cells express considerably lower levels of androgen receptor than LNCaP cells and grow vigorously in androgen deprived condition in vitro, and develop tumors in castrated male mice in vivo. Addition of androgen inhibits cell growth in vitro and tumor growth in vivo. LNCS cells are more resistant to etoposide, a typical apoptotic inducing agent. Although AR signaling is less active in LNCS cells, Stat3 is constitutively activated. Down regulation of Stat3 activation inhibits LNCS cell growth in vitro.

Conclusions: We have developed an androgen-deprivation induced and androgen suppressed human prostate cancer cell line. This cell line is a valuable tool to study molecular mechanisms of the progression of androgen refractory prostate cancer and intermittent androgen suppression therapy.