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Cell Growth & Differentiation Vol. 12, 19-27, January 2001
© 2001 American Association for Cancer Research


Articles

Morphologic Conversion of a Neuroblastoma-derived Cell Line by E6-mediated p53 Degradation1

Supriya V. Gaitonde, Wenqing Qi, Ryan R. Falsey, Neil Sidell and Jesse D. Martinez2

Graduate Program, Cancer Biology Interdisciplinary Program [S. V. G.], and Arizona Cancer Center, Department of Radiation Oncology [W. Q., R. R. F., J. D. M.], University of Arizona, Tucson, Arizona 85724; and Division of Research, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322 [N. S.]

Abstract

Neuroblastoma-derived tumor cells, unlike cells from other tumor types, characteristically express a wild-type but cytoplasmically sequestered p53 protein. To ascertain whether the p53 in these cells retained any physiological activity, we inactivated it in SK-N-SH cells, a neuroblastoma-derived cell line, by introducing the human papilloma virus type 16 E6 expression plasmid. Parent SK-N-SH cell cultures are composed of two cell types exhibiting characteristic morphologies designated neuroblastic (N-type) or substrate-adherent fibroblastic (S-type) cells, both of which have been shown to spontaneously transdifferentiate or interconvert. We report here that down-regulation of p53 resulted in conversion of SK-N-SH cells to the substrate-adherent fibroblast-like S-type cells. The morphologic conversion was accompanied by a loss of neurofilament expression, a marker for the neuronal N-type cells, an increase in the expression of vimentin, and a lack of responsiveness to retinoic acid-induced neuronal differentiation. Importantly, we did not observe N-type cells in the E6-transfected cell population, suggesting that they were incapable of transdifferentiating to the N-type morphology. We also tested the ability of these E6-transfected S-type cells to form colonies in soft agar and observed a markedly reduced capacity of these cells to do so when compared with the parent and mutant E6-transfected cells. These results suggest that p53 is required for the maintenance of the neuroblastic tumorigenic phenotype.




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Proc. Natl. Acad. Sci. USAHome page
L. J. Wainwright, A. Lasorella, and A. Iavarone
Distinct mechanisms of cell cycle arrest control the decision between differentiation and senescence in human neuroblastoma cells
PNAS, July 31, 2001; 98(16): 9396 - 9400.
[Abstract] [Full Text] [PDF]




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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2001 by the American Association of Cancer Research.