The neurotrophin receptor p75NTR is a tumor suppressor in human prostate cancer.
The loss of tumor suppressor gene function contributes to the transformation of human prostate epithelial cells to a malignant pathology. Previous studies have demonstrated a loss of protein expression of the neurotrophin receptor, the p75NTR, from the pathological human prostate. Through cell cycle analysis, we demonstrate that a dose-dependent increase in the expression of p75NTR protein induces increased quiescence of a series of prostate tumor cells in vitro. When the same series of tumor cells were injected into the flanks of SCID mice, the growth of prostate tumors was suppressed in proportion to increased p75NTR expression. Tumor analysis showed that a dose-dependent increase in p75NTR expression was associated with a dose-dependent increase in the proportion of apoptotic cells, as determined by TUNEL assay, and a dose-dependent decrease in the proportion of cells committed to proliferation, as determined by proliferating cell nuclear antigen assay. These results demonstrate that the neurotrophin receptor p75NTR is a tumor suppressor of prostate growth by enhancing cell cycle quiescence, reducing proliferation and increasing apoptosis of the tumor cells.
Krygier
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Department of Biochemistry and Molecular Biology, Johns Hopkins School of Hygiene, Baltimore, MD 21205, USA.
Djakiew
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D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D016193:G1 Phase / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000502:physiology
D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor