EXPRESSION OF PML TUMOR SUPPRESSOR IN A431 CELLS REDUCES CELLULAR GROWTH BY INHIBITING THE EGFR EXPRESSION

Document Type: Regular Paper

Authors

1 Division of genetics, Department of Biology, Faculty of Science, Isfahan University, Isfahan, I. R. of Iran

2 M. D. Anderson Cancer Center, the University of Texas, Houston, Texas, USA

Abstract

Our previous studies showed that the promyelocytic leukemia protein, PML, functions as a
cellular and growth suppressor. Transient expression of PML was also found to repress the activity of the
epidermal growth factor receptor (EGFR) gene promoter. In this study, we have examined the effects of
PML on A431 cells, which express a high level of EGFR protein. The PML gene was introduced into the
cells using the adenovirus-mediated gene transfer system. Western blot analysis on the extracts from the
cells expressing PML showed a significant repression in the expression of the EGFR protein. The cells
were examined for growth and DNA synthesis. The data showed a marked reduction in both growth and
DNA synthesis rate in the cells expressing PML compared with the control cells. Furthermore, in
comparison with the controls, the cells expressing PML were found to be more in G1 phase, fewer in S
and about the same number in the G2/M phase. These data clearly demonstrated that the repression of
EGFR expression in A431 cells by PML was associated with inhibition of cell growth and alteration of
the cell cycle distribution, suggesting a novel mechanism for the known growth inhibitory effects of
PML.

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