Wild-type p53 protein is up-regulated upon cyclic adenosine monophosphate-induced differentiation of human endometrial stromal cells
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Wild-type p53 protein is up-regulated upon cyclic adenosine monophosphate-induced differentiation of human endometrial stromal cells. / Pohnke, Yvonne; Schneider-Merck, Tanja; Fahnenstich, Jasmin; Kempf, Rita; Christian, Mark; Milde-Langosch, Karin; Brosens, Jan J; Gellersen, Birgit.
In: J CLIN ENDOCR METAB, Vol. 89, No. 10, 10.2004, p. 5233-44.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Wild-type p53 protein is up-regulated upon cyclic adenosine monophosphate-induced differentiation of human endometrial stromal cells
AU - Pohnke, Yvonne
AU - Schneider-Merck, Tanja
AU - Fahnenstich, Jasmin
AU - Kempf, Rita
AU - Christian, Mark
AU - Milde-Langosch, Karin
AU - Brosens, Jan J
AU - Gellersen, Birgit
PY - 2004/10
Y1 - 2004/10
N2 - Decidualization of the endometrial stromal compartment is critical for embryo implantation. Initiation of this differentiation process requires elevated intracellular cAMP levels. We now report a massive and sustained up-regulation of p53 tumor suppressor protein during cAMP-induced decidualization of cultured endometrial stromal cells. Nuclear accumulation of p53 was not accompanied by increased mRNA expression, suggesting stabilization of the protein as the underlying mechanism. Proteasomal degradation of p53 is known to be mediated by nuclear Mdm2. Nuclear translocation of Mdm2, in turn, is dependent on phosphorylation by protein kinase B/Akt (PKB/Akt). In cAMP-treated decidualized cells, p53 accumulation was associated with decreased nuclear Mdm2 and cytoplasmic PKB/Akt levels. Conversely, withdrawal of the decidualization stimulus resulted in morphological and biochemical dedifferentiation, disappearance of p53, but increased abundance of PKB/Akt. Furthermore, Western blot and immunohistochemical analyses of endometrial biopsies confirmed that p53 is expressed in vivo in the stromal compartment during the late secretory phase of the cycle. The observation that p53 protein expression is closely associated with decidual transformation indicates a novel role for this tumor suppressor in regulating human endometrial function.
AB - Decidualization of the endometrial stromal compartment is critical for embryo implantation. Initiation of this differentiation process requires elevated intracellular cAMP levels. We now report a massive and sustained up-regulation of p53 tumor suppressor protein during cAMP-induced decidualization of cultured endometrial stromal cells. Nuclear accumulation of p53 was not accompanied by increased mRNA expression, suggesting stabilization of the protein as the underlying mechanism. Proteasomal degradation of p53 is known to be mediated by nuclear Mdm2. Nuclear translocation of Mdm2, in turn, is dependent on phosphorylation by protein kinase B/Akt (PKB/Akt). In cAMP-treated decidualized cells, p53 accumulation was associated with decreased nuclear Mdm2 and cytoplasmic PKB/Akt levels. Conversely, withdrawal of the decidualization stimulus resulted in morphological and biochemical dedifferentiation, disappearance of p53, but increased abundance of PKB/Akt. Furthermore, Western blot and immunohistochemical analyses of endometrial biopsies confirmed that p53 is expressed in vivo in the stromal compartment during the late secretory phase of the cycle. The observation that p53 protein expression is closely associated with decidual transformation indicates a novel role for this tumor suppressor in regulating human endometrial function.
KW - CCAAT-Enhancer-Binding Proteins
KW - Cell Differentiation
KW - Cells, Cultured
KW - Cyclic AMP
KW - Decidua
KW - Female
KW - Humans
KW - Promoter Regions, Genetic
KW - RNA, Messenger
KW - Stromal Cells
KW - Tumor Suppressor Protein p53
KW - Two-Hybrid System Techniques
KW - Up-Regulation
KW - Yeasts
U2 - 10.1210/jc.2004-0012
DO - 10.1210/jc.2004-0012
M3 - SCORING: Journal article
C2 - 15472230
VL - 89
SP - 5233
EP - 5244
JO - J CLIN ENDOCR METAB
JF - J CLIN ENDOCR METAB
SN - 0021-972X
IS - 10
ER -