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Loss of p75 neurotrophin receptor expression accompanies malignant progression to human and murine retinoblastoma
Author(s) -
Dimaras H.,
Coburn B.,
Pajovic S.,
Gallie B.L.
Publication year - 2006
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20179
Subject(s) - retinoblastoma , biology , retina , retinoblastoma protein , retinal , immunohistochemistry , cancer research , apoptosis , tumor progression , low affinity nerve growth factor receptor , receptor , neurotrophin , immunology , gene , genetics , cell cycle , neuroscience , biochemistry
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. © 2006 Wiley‐Liss, Inc.