Expression of p75(NTR) in a human prostate epithelial tumor cell line reduces nerve growth factor-induced cell growth by activation of programmed cell death

Beth Pflug, Daniel Djakiew

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Epithelial expression of the 75-kDa low-affinity neurotrophin receptor (p75(NTR)) is inversely associated with the malignant progression of the human prostate. To elucidate the function of p75(NTR) in the prostate, the human prostate epithelial tumor cell line TSU-pr1, which does not express p75(NTR), was stably and transiently transfected with the cDNA for the receptor. The stably transfected cells were assessed for levels of p75(NTR) expression and categorized into low, intermediate, and high receptor- expressing clones by immunocytochemical and immunoblot analyses. Incorporation of [3H]thymidine was used to assess nerve growth factor (NGF)- induced changes in cell proliferation. TSU-pr1 epithelial cells transfected with a neomycin-resistance vector alone demonstrated a dose-dependent increase in the rate of NGF-stimulated [3H]thymidine uptake. Expression of p75(NTR) decreased the dose-dependent NGF-mediated proliferation of the TSU- pr1 prostate epithelial cells. The greater the degree of expression of p75(NTR) in the transfected clones, the less the stimulatory effect of exogenous NGF on cell proliferation. Furthermore, the ratio of p75(NTR) to tropomyosin receptor kinase for each clone was inversely correlated with the ability of NGF to stimulate growth of the TSU-pr1 transfectants. To determine whether p75(NTR)-mediated growth inhibition of prostate epithelial occurs by induction of programmed cell death, transiently transfected clones were analyzed by an in situ DNA nick-translation assay. NGF deprivation and anti- NGF treatment of transiently transfected TSU-pr1 cells significantly increased the proportion of epithelial cells undergoing programmed cell death by approximately four fold above control levels. Conversely, addition of NGF was able to rescue p75(NTR)-expressing clones from undergoing programmed cell death at levels not significantly different from those of mock-transfected clones. These results demonstrate that p75(NTR) is a negative regulator of human prostate epithelial cell growth by induction of programmed cell death. Hence, loss of p75(NTR) expression on human prostate epithelia eliminates a growth-inhibitory pathway, thereby contributing to the malignant progression of the prostate.

Original languageEnglish (US)
Pages (from-to)106-114
Number of pages9
JournalMolecular Carcinogenesis
Volume23
Issue number2
DOIs
StatePublished - Oct 1998
Externally publishedYes

Fingerprint

Nerve Growth Factor Receptor
Nerve Growth Factor
Tumor Cell Line
Prostate
Cell Death
Epithelial Cells
Growth
Clone Cells
Thymidine
Cell Proliferation

Keywords

  • p75(NTR)
  • Programmed cell death
  • Prostate

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

@article{090e94acbed144a082bb562a1897952b,
title = "Expression of p75(NTR) in a human prostate epithelial tumor cell line reduces nerve growth factor-induced cell growth by activation of programmed cell death",
abstract = "Epithelial expression of the 75-kDa low-affinity neurotrophin receptor (p75(NTR)) is inversely associated with the malignant progression of the human prostate. To elucidate the function of p75(NTR) in the prostate, the human prostate epithelial tumor cell line TSU-pr1, which does not express p75(NTR), was stably and transiently transfected with the cDNA for the receptor. The stably transfected cells were assessed for levels of p75(NTR) expression and categorized into low, intermediate, and high receptor- expressing clones by immunocytochemical and immunoblot analyses. Incorporation of [3H]thymidine was used to assess nerve growth factor (NGF)- induced changes in cell proliferation. TSU-pr1 epithelial cells transfected with a neomycin-resistance vector alone demonstrated a dose-dependent increase in the rate of NGF-stimulated [3H]thymidine uptake. Expression of p75(NTR) decreased the dose-dependent NGF-mediated proliferation of the TSU- pr1 prostate epithelial cells. The greater the degree of expression of p75(NTR) in the transfected clones, the less the stimulatory effect of exogenous NGF on cell proliferation. Furthermore, the ratio of p75(NTR) to tropomyosin receptor kinase for each clone was inversely correlated with the ability of NGF to stimulate growth of the TSU-pr1 transfectants. To determine whether p75(NTR)-mediated growth inhibition of prostate epithelial occurs by induction of programmed cell death, transiently transfected clones were analyzed by an in situ DNA nick-translation assay. NGF deprivation and anti- NGF treatment of transiently transfected TSU-pr1 cells significantly increased the proportion of epithelial cells undergoing programmed cell death by approximately four fold above control levels. Conversely, addition of NGF was able to rescue p75(NTR)-expressing clones from undergoing programmed cell death at levels not significantly different from those of mock-transfected clones. These results demonstrate that p75(NTR) is a negative regulator of human prostate epithelial cell growth by induction of programmed cell death. Hence, loss of p75(NTR) expression on human prostate epithelia eliminates a growth-inhibitory pathway, thereby contributing to the malignant progression of the prostate.",
keywords = "p75(NTR), Programmed cell death, Prostate",
author = "Beth Pflug and Daniel Djakiew",
year = "1998",
month = "10",
doi = "10.1002/(SICI)1098-2744(199810)23:2<106::AID-MC7>3.0.CO;2-W",
language = "English (US)",
volume = "23",
pages = "106--114",
journal = "Molecular Carcinogenesis",
issn = "0899-1987",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Expression of p75(NTR) in a human prostate epithelial tumor cell line reduces nerve growth factor-induced cell growth by activation of programmed cell death

AU - Pflug, Beth

AU - Djakiew, Daniel

PY - 1998/10

Y1 - 1998/10

N2 - Epithelial expression of the 75-kDa low-affinity neurotrophin receptor (p75(NTR)) is inversely associated with the malignant progression of the human prostate. To elucidate the function of p75(NTR) in the prostate, the human prostate epithelial tumor cell line TSU-pr1, which does not express p75(NTR), was stably and transiently transfected with the cDNA for the receptor. The stably transfected cells were assessed for levels of p75(NTR) expression and categorized into low, intermediate, and high receptor- expressing clones by immunocytochemical and immunoblot analyses. Incorporation of [3H]thymidine was used to assess nerve growth factor (NGF)- induced changes in cell proliferation. TSU-pr1 epithelial cells transfected with a neomycin-resistance vector alone demonstrated a dose-dependent increase in the rate of NGF-stimulated [3H]thymidine uptake. Expression of p75(NTR) decreased the dose-dependent NGF-mediated proliferation of the TSU- pr1 prostate epithelial cells. The greater the degree of expression of p75(NTR) in the transfected clones, the less the stimulatory effect of exogenous NGF on cell proliferation. Furthermore, the ratio of p75(NTR) to tropomyosin receptor kinase for each clone was inversely correlated with the ability of NGF to stimulate growth of the TSU-pr1 transfectants. To determine whether p75(NTR)-mediated growth inhibition of prostate epithelial occurs by induction of programmed cell death, transiently transfected clones were analyzed by an in situ DNA nick-translation assay. NGF deprivation and anti- NGF treatment of transiently transfected TSU-pr1 cells significantly increased the proportion of epithelial cells undergoing programmed cell death by approximately four fold above control levels. Conversely, addition of NGF was able to rescue p75(NTR)-expressing clones from undergoing programmed cell death at levels not significantly different from those of mock-transfected clones. These results demonstrate that p75(NTR) is a negative regulator of human prostate epithelial cell growth by induction of programmed cell death. Hence, loss of p75(NTR) expression on human prostate epithelia eliminates a growth-inhibitory pathway, thereby contributing to the malignant progression of the prostate.

AB - Epithelial expression of the 75-kDa low-affinity neurotrophin receptor (p75(NTR)) is inversely associated with the malignant progression of the human prostate. To elucidate the function of p75(NTR) in the prostate, the human prostate epithelial tumor cell line TSU-pr1, which does not express p75(NTR), was stably and transiently transfected with the cDNA for the receptor. The stably transfected cells were assessed for levels of p75(NTR) expression and categorized into low, intermediate, and high receptor- expressing clones by immunocytochemical and immunoblot analyses. Incorporation of [3H]thymidine was used to assess nerve growth factor (NGF)- induced changes in cell proliferation. TSU-pr1 epithelial cells transfected with a neomycin-resistance vector alone demonstrated a dose-dependent increase in the rate of NGF-stimulated [3H]thymidine uptake. Expression of p75(NTR) decreased the dose-dependent NGF-mediated proliferation of the TSU- pr1 prostate epithelial cells. The greater the degree of expression of p75(NTR) in the transfected clones, the less the stimulatory effect of exogenous NGF on cell proliferation. Furthermore, the ratio of p75(NTR) to tropomyosin receptor kinase for each clone was inversely correlated with the ability of NGF to stimulate growth of the TSU-pr1 transfectants. To determine whether p75(NTR)-mediated growth inhibition of prostate epithelial occurs by induction of programmed cell death, transiently transfected clones were analyzed by an in situ DNA nick-translation assay. NGF deprivation and anti- NGF treatment of transiently transfected TSU-pr1 cells significantly increased the proportion of epithelial cells undergoing programmed cell death by approximately four fold above control levels. Conversely, addition of NGF was able to rescue p75(NTR)-expressing clones from undergoing programmed cell death at levels not significantly different from those of mock-transfected clones. These results demonstrate that p75(NTR) is a negative regulator of human prostate epithelial cell growth by induction of programmed cell death. Hence, loss of p75(NTR) expression on human prostate epithelia eliminates a growth-inhibitory pathway, thereby contributing to the malignant progression of the prostate.

KW - p75(NTR)

KW - Programmed cell death

KW - Prostate

UR - http://www.scopus.com/inward/record.url?scp=0031595996&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031595996&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-2744(199810)23:2<106::AID-MC7>3.0.CO;2-W

DO - 10.1002/(SICI)1098-2744(199810)23:2<106::AID-MC7>3.0.CO;2-W

M3 - Article

C2 - 9808164

AN - SCOPUS:0031595996

VL - 23

SP - 106

EP - 114

JO - Molecular Carcinogenesis

JF - Molecular Carcinogenesis

SN - 0899-1987

IS - 2

ER -