Loss of p75 neurotrophin receptor expression accompanies malignant progression to human and murine retinoblastoma

Authors

  • H. Dimaras,

    1. Department of Molecular and Medical Genetics, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada
    2. Division of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada
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  • B. Coburn,

    1. Department of Molecular and Medical Genetics, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada
    2. Division of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada
    Current affiliation:
    1. Michael Smith Laboratories, University of British Columbia, #301- 2185 East Mall Vancouver, BC, Canada V6T 1Z4.
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  • S. Pajovic,

    1. Division of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada
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  • B.L. Gallie

    Corresponding author
    1. Department of Molecular and Medical Genetics, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada
    2. Department of Ophthalmology, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada
    3. Division of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada
    • Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
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Abstract

We studied the expression of pro-apoptotic neurotrophin receptor p75 (p75NTR) in human and murine retinoblastoma, compared to normal retina, and examined changes in p75NTR 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 p75NTR mRNA, compared to human retina. Moreover, p75NTR protein was not detected in any tumor studied, unlike normal retina. Like human retinoblastoma, advanced murine retinoblastoma did not express p75NTR. However, before tumors emerged, small clusters of TAg-positive cells coexpressed p75NTR 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 p75NTR protein, while the retinoblastoma did not. We suggest that p75NTR loss accompanies progression from retinoma to retinoblastoma. © 2006 Wiley-Liss, Inc.

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