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 language | English (US) |
|---|---|
| Pages (from-to) | 106-114 |
| Number of pages | 9 |
| Journal | Molecular Carcinogenesis |
| Volume | 23 |
| Issue number | 2 |
| DOIs | |
| State | Published - Oct 1998 |
| Externally published | Yes |
Fingerprint
Keywords
- p75(NTR)
- Programmed cell death
- Prostate
ASJC Scopus subject areas
- Cancer Research
- Molecular Biology
Cite this
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. / Pflug, Beth; Djakiew, Daniel.
In: Molecular Carcinogenesis, Vol. 23, No. 2, 10.1998, p. 106-114.Research output: Contribution to journal › Article
}
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
VL - 23
SP - 106
EP - 114
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
SN - 0899-1987
IS - 2
ER -