NF-κB2/p52 enhances androgen-independent growth of human LNCaP cells via protection from apoptotic cell death and cell cycle arrest induced by androgen-deprivation

Nagalakshmi Nadiminty, Jae Yeon Chun, Wei Lou, Xin Lin, Allen C Gao

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

PURPOSE. Androgen-deprivation therapy only causes a temporary regression of prostate cancer, as all tumors will eventually progress to refractory to hormonal therapy after 1-3 years of treatment. The underlying mechanisms of prostate cancer androgen refractory progression are incompletely understood. In this study, we employed in vitro as well as in vivo models to examine the role of NF-κB2/p52 in prostate cancer growth and androgen independent progression. EXPERIMENTAL DESIGN. The effects of NF-κB2/p52 on cell growth, androgen responsiveness, cell cycle and apoptosis were examined in androgen sensitive LNCaP cells. The effect of NF-κB2/p52 on tumor growth was examined in intact and castrated male mice. RESULTS. Overexpression of NF-κB2/p52 enhances androgen-sensitive LNCaP human prostate cancer cell growth and clonogenic ability in androgen-deprived condition in vitro. NF-κB2/p52 induced androgen-independent growth is through protecting LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. In addition, NF-κB2/p52 stimulates Cyclin D1 expression and knock down of Cyclin D1 expression by siRNA abolished NF-κB2/p52-induced cell growth in vitro. Adenoviral mediated NF-κB2/p52 expression in LNCaP cells enhances tumor growth in intact male nude mice and induces tumor growth in castrated male nude mice, suggesting that overexpression of NF-κB2/p52 induces androgen-independent growth of androgen-sensitive LNCaP cells. CONCLUSIONS. Overexpression of NF-κB2/p52 protects androgen sensitive LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. NF-κB2/p52 activation induces androgen-independent growth in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)1725-1733
Number of pages9
JournalProstate
Volume68
Issue number16
DOIs
StatePublished - Dec 1 2008

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Cytoprotection
Cell Cycle Checkpoints
Androgens
Cell Death
Growth
Prostatic Neoplasms
Cyclin D1
Nude Mice
Neoplasms
Small Interfering RNA

Keywords

  • Androgen-independence
  • NF-κB2/p52
  • Prostate

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

Cite this

NF-κB2/p52 enhances androgen-independent growth of human LNCaP cells via protection from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. / Nadiminty, Nagalakshmi; Chun, Jae Yeon; Lou, Wei; Lin, Xin; Gao, Allen C.

In: Prostate, Vol. 68, No. 16, 01.12.2008, p. 1725-1733.

Research output: Contribution to journalArticle

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abstract = "PURPOSE. Androgen-deprivation therapy only causes a temporary regression of prostate cancer, as all tumors will eventually progress to refractory to hormonal therapy after 1-3 years of treatment. The underlying mechanisms of prostate cancer androgen refractory progression are incompletely understood. In this study, we employed in vitro as well as in vivo models to examine the role of NF-κB2/p52 in prostate cancer growth and androgen independent progression. EXPERIMENTAL DESIGN. The effects of NF-κB2/p52 on cell growth, androgen responsiveness, cell cycle and apoptosis were examined in androgen sensitive LNCaP cells. The effect of NF-κB2/p52 on tumor growth was examined in intact and castrated male mice. RESULTS. Overexpression of NF-κB2/p52 enhances androgen-sensitive LNCaP human prostate cancer cell growth and clonogenic ability in androgen-deprived condition in vitro. NF-κB2/p52 induced androgen-independent growth is through protecting LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. In addition, NF-κB2/p52 stimulates Cyclin D1 expression and knock down of Cyclin D1 expression by siRNA abolished NF-κB2/p52-induced cell growth in vitro. Adenoviral mediated NF-κB2/p52 expression in LNCaP cells enhances tumor growth in intact male nude mice and induces tumor growth in castrated male nude mice, suggesting that overexpression of NF-κB2/p52 induces androgen-independent growth of androgen-sensitive LNCaP cells. CONCLUSIONS. Overexpression of NF-κB2/p52 protects androgen sensitive LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. NF-κB2/p52 activation induces androgen-independent growth in vitro and in vivo.",
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T1 - NF-κB2/p52 enhances androgen-independent growth of human LNCaP cells via protection from apoptotic cell death and cell cycle arrest induced by androgen-deprivation

AU - Nadiminty, Nagalakshmi

AU - Chun, Jae Yeon

AU - Lou, Wei

AU - Lin, Xin

AU - Gao, Allen C

PY - 2008/12/1

Y1 - 2008/12/1

N2 - PURPOSE. Androgen-deprivation therapy only causes a temporary regression of prostate cancer, as all tumors will eventually progress to refractory to hormonal therapy after 1-3 years of treatment. The underlying mechanisms of prostate cancer androgen refractory progression are incompletely understood. In this study, we employed in vitro as well as in vivo models to examine the role of NF-κB2/p52 in prostate cancer growth and androgen independent progression. EXPERIMENTAL DESIGN. The effects of NF-κB2/p52 on cell growth, androgen responsiveness, cell cycle and apoptosis were examined in androgen sensitive LNCaP cells. The effect of NF-κB2/p52 on tumor growth was examined in intact and castrated male mice. RESULTS. Overexpression of NF-κB2/p52 enhances androgen-sensitive LNCaP human prostate cancer cell growth and clonogenic ability in androgen-deprived condition in vitro. NF-κB2/p52 induced androgen-independent growth is through protecting LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. In addition, NF-κB2/p52 stimulates Cyclin D1 expression and knock down of Cyclin D1 expression by siRNA abolished NF-κB2/p52-induced cell growth in vitro. Adenoviral mediated NF-κB2/p52 expression in LNCaP cells enhances tumor growth in intact male nude mice and induces tumor growth in castrated male nude mice, suggesting that overexpression of NF-κB2/p52 induces androgen-independent growth of androgen-sensitive LNCaP cells. CONCLUSIONS. Overexpression of NF-κB2/p52 protects androgen sensitive LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. NF-κB2/p52 activation induces androgen-independent growth in vitro and in vivo.

AB - PURPOSE. Androgen-deprivation therapy only causes a temporary regression of prostate cancer, as all tumors will eventually progress to refractory to hormonal therapy after 1-3 years of treatment. The underlying mechanisms of prostate cancer androgen refractory progression are incompletely understood. In this study, we employed in vitro as well as in vivo models to examine the role of NF-κB2/p52 in prostate cancer growth and androgen independent progression. EXPERIMENTAL DESIGN. The effects of NF-κB2/p52 on cell growth, androgen responsiveness, cell cycle and apoptosis were examined in androgen sensitive LNCaP cells. The effect of NF-κB2/p52 on tumor growth was examined in intact and castrated male mice. RESULTS. Overexpression of NF-κB2/p52 enhances androgen-sensitive LNCaP human prostate cancer cell growth and clonogenic ability in androgen-deprived condition in vitro. NF-κB2/p52 induced androgen-independent growth is through protecting LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. In addition, NF-κB2/p52 stimulates Cyclin D1 expression and knock down of Cyclin D1 expression by siRNA abolished NF-κB2/p52-induced cell growth in vitro. Adenoviral mediated NF-κB2/p52 expression in LNCaP cells enhances tumor growth in intact male nude mice and induces tumor growth in castrated male nude mice, suggesting that overexpression of NF-κB2/p52 induces androgen-independent growth of androgen-sensitive LNCaP cells. CONCLUSIONS. Overexpression of NF-κB2/p52 protects androgen sensitive LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. NF-κB2/p52 activation induces androgen-independent growth in vitro and in vivo.

KW - Androgen-independence

KW - NF-κB2/p52

KW - Prostate

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