![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 56, Issue 5, 966-972, November 1999
Program for Molecular Pharmacology and Therapeutics, Memorial
Sloan-Kettering Cancer Center, New York, New York
A stable transfectant (S2SN7) of p53-null SaOS-2 (human osteosarcoma)
cells expressing wild-type p53 under the tight control of a
tetracycline-responsive promoter was used to study the
functional roles of p53 in cellular response to cisplatinum (CP). When
cells were grown in media containing normal concentrations (10%) of serum, induction of p53 by tetracycline withdrawal resulted in an
8-fold decrease in sensitivity to CP. In contrast, when cells were
grown in lower serum (1%) media, induction of p53 led to a 10-fold
increase in sensitivity to CP. The p53-mediated sensitivity to CP under
lower serum conditions was attributed, at least in part, to increased
susceptibility of p53-mediated apoptosis. Under lower serum (0.1-1%)
but not normal serum conditions, p53 induction correlated with
selective down-regulation of bcl-2, an inhibitor of apoptosis. In
addition, a host-cell reactivation assay showed that induction of p53
caused a significant increase in repair of CP-induced DNA damage under
normal serum but not low serum conditions. These data suggest that
growth conditions may modulate and possibly reverse p53-mediated CP
sensitivity by altering p53-mediated gene regulation and, as a result,
susceptibility to apoptosis. They also suggest that a combined effect
of p53-mediated apoptosis and DNA repair may be the ultimate
determinant in p53-mediated cellular resistance or sensitivity to
chemotherapeutic drugs.
This article has been cited by other articles:
|
|
 |
|
  S. Bhana, A. Hewer, D. H. Phillips, and D. R. Lloyd p53-dependent global nucleotide excision repair of cisplatin-induced intrastrand cross links in human cells Mutagenesis, March 1, 2008; 23(2): 131 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhana and D. R. Lloyd The role of p53 in DNA damage-mediated cytotoxicity overrides its ability to regulate nucleotide excision repair in human fibroblasts Mutagenesis, January 1, 2008; 23(1): 43 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Lin and S. B. Howell DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance Mol. Cancer Ther., May 1, 2006; 5(5): 1239 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kampa, C. Kogia, P. A. Theodoropoulos, P. Anezinis, I. Charalampopoulos, E. A. Papakonstanti, E. N. Stathopoulos, A. Hatzoglou, C. Stournaras, A. Gravanis, et al. Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells Mol. Cancer Ther., May 1, 2006; 5(5): 1342 - 1351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E.M. Vickers, K. Rose, R. Fisher, M. Saulnier, P. Sahota, and P. Bentley Kidney Slices of Human and Rat to Characterize Cisplatin-Induced Injury on Cellular Pathways and Morphology Toxicol Pathol, August 1, 2004; 32(5): 577 - 590. [Abstract] [PDF]
|
|
|
|
 |
|
 B. H. Hoang, T. Kubo, J. H. Healey, R. Yang, S. S. Nathan, E. A. Kolb, B. Mazza, P. A. Meyers, and R. Gorlick Dickkopf 3 Inhibits Invasion and Motility of Saos-2 Osteosarcoma Cells by Modulating the Wnt-{beta}-Catenin Pathway Cancer Res., April 15, 2004; 64(8): 2734 - 2739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wu, W. Fan, S. Xu, and Y. Zhou Sensitization to the Cytotoxicity of Cisplatin by Transfection with Nucleotide Excision Repair Gene Xeroderma Pigmentosun Group A Antisense RNA in Human Lung Adenocarcinoma Cells Clin. Cancer Res., December 1, 2003; 9(16): 5874 - 5879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Kim, M. Blake, J. H. Baek, G. Kohlhagen, Y. Pommier, and F. Carrier Inhibition of Histone Deacetylase Increases Cytotoxicity to Anticancer Drugs Targeting DNA Cancer Res., November 1, 2003; 63(21): 7291 - 7300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, A. J. Raffo, L. Drew, Y. Mao, A. Tran, D. P. Petrylak, and R. L. Fine Fas-Mediated Apoptosis Is Dependent on Wild-Type p53 Status in Human Cancer Cells Expressing a Temperature-Sensitive p53 Mutant Alanine-143 Cancer Res., April 1, 2003; 63(7): 1527 - 1533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Petit, D. J. Bearss, D. A. Troyer, R. M. Munoz, and J. J. Windle p53-independent Response to Cisplatin and Oxaliplatin in MMTV-ras Mouse Salivary Tumors Mol. Cancer Ther., February 1, 2003; 2(2): 165 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Koivusalo, E. Krausz, P. Ruotsalainen, H. Helenius, and S. Hietanen Chemoradiation of Cervical Cancer Cells: Targeting Human Papillomavirus E6 and p53 Leads to Either Augmented or Attenuated Apoptosis Depending on the Platinum Carrier Ligand Cancer Res., December 15, 2002; 62(24): 7364 - 7371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Hershberger, T. F. McGuire, W.-D. Yu, E. G. Zuhowski, J. H. M. Schellens, M. J. Egorin, D. L. Trump, and C. S. Johnson Cisplatin Potentiates 1,25-Dihydroxyvitamin D3-induced Apoptosis in Association with Increased Mitogen-activated Protein Kinase Kinase Kinase 1 (MEKK-1) Expression Mol. Cancer Ther., August 1, 2002; 1(10): 821 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Smith and Y. R. Seo p53 regulation of DNA excision repair pathways Mutagenesis, March 1, 2002; 17(2): 149 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Lin, K. Ramamurthi, M. Mishima, A. Kondo, R. D. Christen, and S. B. Howell p53 Modulates the Effect of Loss of DNA Mismatch Repair on the Sensitivity of Human Colon Cancer Cells to the Cytotoxic and Mutagenic Effects of Cisplatin Cancer Res., February 1, 2001; 61(4): 1508 - 1516. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
