Functional Link Between Glucocorticoid Hormones and the TP53 Tumor Suppressor Gene in a Rat Glioma Cell Model

Author(s)

Antero Ferreira de Almeida Macedo

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2007-10-02

Examining board members

Mari Cleide Sogayar; José Alexandre Marzagao Barbuto; Suely Lopes Gomes; Robert Schumacher; Bryan Eric Strauss

• Advisor: Mari Cleide Sogayar

Abstract

Both glucocorticoid hormones (GCs) and the TP53 tumor suppressor gene mediate cellular responses to a diversity of physiological stress conditions, acting as crucial regulators of the life/death process in a wide variety of cell types. The ST1/P7 rat glioma model cell system is particularly interesting to investigate the role of p53 in the action of GCs, since these cell lines display opposite responses to GCs. Treatment with Hydrocortisone (Hy) leads ST1 cells to a complete tumoral→normal phenotypic reversion, while P7 cells are highly resistant to this treatment. It was possible to observe that activation of p53 by Hy occurs only in ST1 cells, but not in GC-resistant P7 cells. This activation is mediated by induction of phosphorylation of the Ser15 residue of p53 and its accumulation in the nucleus, resulting in increased binding of p53 to its responsive elements on the DNA and in activation of its transactivating potential, leading to increased expression of some of its target genes. However, blocking of p53 through siRNA was not sufficient to alter ST1 cells response to GCs, indicating that the positive regulation of p53 by GCs may be a secondary, non-essential, event for the anti-tumor response exerted by these hormones in ST1 cells. (AU)