Loss of p75 neurotrophin receptor expression accompanies malignant progression to human and murine retinoblastoma.
We studied the expression of pro-apoptotic neurotrophin receptor p75 (p75(NTR)) in human and murine retinoblastoma, compared to normal retina, and examined changes in p75(NTR) expression with the onset of apoptosis in the course of murine retinoblastoma progression, using immunohistochemistry and quantitative real-time RT-PCR. The murine retinoblastoma is induced by retinal specific expression of SV40 T-antigen (TAg), which blocks the function of the retinoblastoma protein (pRB) and related proteins, and is a well-studied model that closely simulates human retinoblastoma. The majority of human retinoblastoma either lacked or expressed decreased levels of p75(NTR) mRNA, compared to human retina. Moreover, p75(NTR) protein was not detected in any tumor studied, unlike normal retina. Like human retinoblastoma, advanced murine retinoblastoma did not express p75(NTR). However, before tumors emerged, small clusters of TAg-positive cells coexpressed p75(NTR) and activated caspase-3, a marker of apoptosis. Furthermore, in three rare human eyes containing retinoblastoma adjacent to regions resembling the benign retinal tumor retinoma, both normal retina and retinoma-like tissue expressed p75(NTR) protein, while the retinoblastoma did not. We suggest that p75(NTR) loss accompanies progression from retinoma to retinoblastoma.
Department of Molecular and Medical Genetics, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada.
H
H
Dimaras
B
B
Coburn
S
S
Pajovic
B L
BL
Gallie
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism; D019572:Retinal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D020800:Receptor, Nerve Growth Factor; D016160:Retinoblastoma Protein; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases