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Cancer Biol Ther. 2002 Nov-Dec;1(6):665-8.

The histone deacetylase inhibitor FR901228 (desipeptide) restores expression and function of pseudo-null p53.

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Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.


We have previously described a novel mechanism of p53 dysfunction, characterized by repression of mRNA and protein expression effectively leading to functional inactivation of wt p53 in SW-1736 human anaplastic thyroid cancer cells (pseudo-null p53). Here we demonstrated that treatment of SW-1736 cells with sub-cytotoxic concentrations of FR901228, a histone deacetylase (HDAC) inhibitor, results in marked induction of p53 mRNA and protein. The p53 induced by FR901228 was functional as evidenced by mdm-2 and p21 transactivation, and its further accumulation following DNA damage by doxorubicin. Furthermore, pretreatment with FR901228 sensitized SW-1736 cells to doxorubicin. This study validates the concept of pseudo-null p53, as a mechanism of p53 inactivation, and demonstrates that pseudo-null p53 can be rescued pharmacologically.

[Indexed for MEDLINE]

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