© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 1530-1536, Copyright © 1997 by Oxford University Press
CL Schlamp, GL Poulsen, TM Nork and RW Nickells
BACKGROUND: Retinoblastoma is the most common childhood tumor of the eye,
arising from cells that are defective in both copies of the retinoblastoma
susceptibility gene (RB1). Most retinoblastoma tumor cells eventually
undergo programmed cell death (i.e., apoptosis); however, some cells can
acquire the ability to metastasize and become immortal. Transfection of
immortal retinoblastoma cells with DNA sequences encoding wild-type p53
protein induces cell death, suggesting that the loss of both RB1 and p53
functions may be required for cell immortalization. We have examined this
possibility by characterizing the p53 protein and messenger RNA in six
independently isolated, immortalized retinoblastoma cell lines. METHODS:
Western blotting methods were used to assess p53 protein level in each cell
line, and Cleavase Fragment-Length Polymorphism analysis of complementary
DNAs was used to screen for mutations in p53 messenger RNA. Localization of
p53 protein in cells of the immortalized lines and in specimens of
retinoblastoma tumors was achieved by means of indirect immunofluorescence
and immunocytochemistry, respectively. RESULTS: All six immortalized cell
lines expressed wild-type p53 messenger RNA and high levels of p53 protein.
Although p53 is normally a nuclear protein, the p53 in four of the six cell
lines was located predominately in the cytoplasm; in the remaining two cell
lines, p53 was localized in both the nucleus and the cytoplasm. Cytoplasmic
localization of p53 in retinoblastoma tumor specimens was rare and usually
restricted to cells that had invaded adjacent ocular tissues, indicative of
the early stages of metastasis. CONCLUSIONS: Some immortalized
retinoblastoma cells may exhibit p53 dysfunction through nuclear exclusion
of wild- type p53 protein.
ARTICLES
Nuclear exclusion of wild-type p53 in immortalized human retinoblastoma cells
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison 53792, USA.
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