Establishment of ponasterone A-inducible the wild-type p53 protein-expressing clones from HSC-1 cells, cell growth suppression by p53 expression and the suppression mechanism

2008 ◽  
Vol 301 (9) ◽  
pp. 631-646 ◽  
Author(s):  
Makoto Hori ◽  
Keiji Suzuki ◽  
Masako U. Udono ◽  
Motohiro Yamauchi ◽  
Mariko Mine ◽  
...  
Keyword(s):  
Cell Growth ◽  
P53 Protein ◽  
Growth Suppression ◽  
Wild Type ◽  
P53 Expression ◽  
Suppression Mechanism ◽  
Wild Type P53 ◽  
Cell Growth Suppression ◽  
Ponasterone A

scholarly journals An MDM2 inhibitor achieves synergistic cytotoxic effects with adenoviruses lacking E1B55kDa gene on mesothelioma with the wild-type p53 through augmenting NFI expression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Thao Thi Thanh Nguyen ◽  
Masato Shingyoji ◽  
Michiko Hanazono ◽  
Boya Zhong ◽  
Takao Morinaga ◽  
...  
Keyword(s):  
Wild Type ◽  
Inhibitory Effects ◽  
Cytotoxic Effects ◽  
P53 Expression ◽  
Nuclear Factor I ◽  
Infected Cells ◽  
Wild Type P53 ◽  
Mdm2 Inhibitor ◽  
P16 Expression

AbstractA majority of mesothelioma specimens were defective of p14 and p16 expression due to deletion of the INK4A/ARF region, and the p53 pathway was consequently inactivated by elevated MDM2 functions which facilitated p53 degradaton. We investigated a role of p53 elevation by MDM2 inhibitors, nutlin-3a and RG7112, in cytotoxicity of replication-competent adenoviruses (Ad) lacking the p53-binding E1B55kDa gene (Ad-delE1B). We found that a growth inhibition by p53-activating Ad-delE1B was irrelevant to p53 expression in the infected cells, but combination of Ad-delE1B and the MDM2 inhibitor produced synergistic inhibitory effects on mesothelioma with the wild-type but not mutated p53 genotype. The combination augmented p53 phosphorylation, activated apoptotic but not autophagic pathway, and enhanced DNA damage signals through ATM-Chk2 phosphorylation. The MDM2 inhibitors facilitated production of the Ad progenies through augmented expression of nuclear factor I (NFI), one of the transcriptional factors involved in Ad replications. Knocking down of p53 with siRNA did not increase the progeny production or the NFI expression. We also demonstrated anti-tumor effects by the combination of Ad-delE1B and the MDM2 inhibitors in an orthotopic animal model. These data collectively indicated that upregulation of wild-type p53 expression contributed to cytotoxicity by E1B55kDa-defective replicative Ad through NFI induction and suggested that replication-competent Ad together with augmented p53 levels was a therapeutic strategy for p53 wild-type mesothelioma.

Adenovirus-mediated wild-type P53 expression suppresses growth of lung adeno-carcinoma cells

1998 ◽  
Vol 10 (3) ◽  
pp. 178-181
Author(s):  
Jian Li ◽  
Yongjing Xia ◽  
Lei Jiang ◽  
Hongxia Li ◽  
Yajun Hu ◽  
...  
Keyword(s):  
Carcinoma Cells ◽  
Wild Type ◽  
P53 Expression ◽  
Wild Type P53 ◽  
Adeno Carcinoma

Human p53 and CDC2Hs genes combine to inhibit the proliferation of Saccharomyces cerevisiae

1992 ◽  
Vol 12 (3) ◽  
pp. 1357-1365
Author(s):  
J M Nigro ◽  
R Sikorski ◽  
S I Reed ◽  
B Vogelstein
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Growth Inhibition ◽  
Mammalian Cells ◽  
P53 Protein ◽  
Inducible Promoter ◽  
Mutant P53 ◽  
Wild Type ◽  
Growth Inhibitory Activity ◽  
Wild Type P53 ◽  
P53 Genes

Human wild-type and mutant p53 genes were expressed under the control of a galactose-inducible promoter in Saccharomyces cerevisiae. The growth rate of the yeast was reduced in cells expressing wild-type p53, whereas cells transformed with mutant p53 genes derived from human tumors were less affected. Coexpression of the normal p53 protein with the human cell cycle-regulated protein kinase CDC2Hs resulted in much more pronounced growth inhibition that for p53 alone. Cells expressing p53 and CDC2Hs were partially arrested in G1, as determined by morphological analysis and flow cytometry. p53 was phosphorylated when expressed in the yeast, but differences in phosphorylation did not explain the growth inhibition attributable to coexpression of p53 and CDC2Hs. These results suggest that wild-type p53 has a growth-inhibitory activity in S. cerevisiae similar to that observed in mammalian cells and suggests that this yeast may provide a useful model for defining the pathways through which p53 acts.

scholarly journals Tumor Eradication by Wild-type p53-specific Cytotoxic T Lymphocytes

1997 ◽  
Vol 186 (5) ◽  
pp. 695-704 ◽  
Author(s):  
Michel P.M. Vierboom ◽  
Hans W. Nijman ◽  
Rienk Offringa ◽  
Ellen I.H. van der Voort ◽  
Thorbald van Hall ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Normal Tissue ◽  
P53 Protein ◽  
P53 Gene ◽  
Wild Type ◽  
Wild Type P53 ◽  
Tumor Outgrowth ◽  
Tumor Eradication

The tumor suppressor protein p53 is overexpressed in close to 50% of all human malignancies. The p53 protein is therefore an attractive target for immunotherapy. Cytotoxic T lymphocytes (CTLs) recognizing a murine wild-type p53 peptide, presented by the major histocompatibility complex class I molecule H-2Kb, were generated by immunizing p53 gene deficient (p53 −/−) C57BL/6 mice with syngeneic p53-overexpressing tumor cells. Adoptive transfer of these CTLs into tumor-bearing p53 +/+ nude mice caused complete and permanent tumor eradication. Importantly, this occurred in the absence of any demonstrable damage to normal tissue. When transferred into p53 +/+ immunocompetent C57BL/6 mice, the CTLs persisted for weeks in the absence of immunopathology and were capable of preventing tumor outgrowth. Wild-type p53-specific CTLs can apparently discriminate between p53-overexpressing tumor cells and normal tissue, indicating that widely expressed autologous molecules such as p53 can serve as a target for CTL-mediated immunotherapy of tumors.

Release of an inhibitor of angiogenesis upon induction of wild type p53 expression in glioblastoma cells

1994 ◽  
Vol 8 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Erwin G. Van Meir ◽  
Peter J. Polverini ◽  
Victoria R. Chazin ◽  
H.-J. Su Huang ◽  
Nicolas de Tribolet ◽  
...  
Keyword(s):  
Wild Type ◽  
Glioblastoma Cells ◽  
P53 Expression ◽  
Wild Type P53

Tumor Cell Growth Suppression by Chalcone (1,3-Diphenyl-2-Propen-l-One)

1997 ◽  
Vol 12 (1) ◽  
pp. 51-54 ◽  
Author(s):  
Hideo Kamei ◽  
Tatsurou Koide ◽  
Yoko Hashimoto ◽  
Takashi Kojima ◽  
Makoto Hasegawa
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Growth Suppression ◽  
Tumor Cell Growth ◽  
Cell Growth Suppression
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