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Citations to this article

Regulation of expression of the multidrug resistance protein MRP1 by p53 in human prostate cancer cells
Gregory F. Sullivan, … , Judy Bash-Babula, William N. Hait
Gregory F. Sullivan, … , Judy Bash-Babula, William N. Hait
Published May 1, 2000
Citation Information: J Clin Invest. 2000;105(9):1261-1267. https://doi.org/10.1172/JCI9290.
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Regulation of expression of the multidrug resistance protein MRP1 by p53 in human prostate cancer cells

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Abstract

The expression of several drug-resistance genes, including MRP and p53, increases with advancing stage of human prostate cancer. Altered transcription could account for the genotypic alterations associated with prostate cancer progression, and it was recently reported that the promoter of MRP1 is activated in the presence of mutant p53. To determine whether there is a relationship between p53 status and the expression of MRP1, a human, temperature-sensitive p53 mutant (tsp Val138) was transfected into LNCaP human prostate cancer cells. In the transfected cell line (LVCaP), the wild-type p53 produced growth arrest at the G1/S interface of the cell cycle, inhibited colony formation, and induced p21waf1/cip1. Temperature shifting to 38°C (p53 mutant) produced a time-dependent increase in expression of MRP1. This change in MRP1 expression was also seen in isogenic cell lines in which p53 was inactivated by human papilloma virus (HPV)16E6 protein or by a dominant-negative mutant. Functional assays revealed a decrease in drug accumulation and drug sensitivity associated with mutant p53 and increased MRP1 expression. These results provide the first mechanistic link between expression of MRP1 and mutation of p53 in human prostate cancer and support recent clinical associations. Furthermore, these data suggest a mechanism tying accumulation of p53 mutations to the multidrug resistance phenotype seen in this disease.

Authors

Gregory F. Sullivan, Jin-Ming Yang, Andrew Vassil, Jun Yang, Judy Bash-Babula, William N. Hait

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Total citations by year

Year: 2023 2022 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 Total
Citations: 1 1 3 2 3 1 1 4 4 2 3 4 6 5 3 5 5 4 5 7 8 6 1 84
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Citations to this article in year 2014 (4)

Title and authors Publication Year
A cisplatin-resistant head and neck cancer cell line with cytoplasmic p53(mut) exhibits ATP-binding cassette transporter upregulation and high glutathione levels
M Tonigold, A Rossmann, M Meinold, M Bette, M Märken, K Henkenius, AC Bretz, G Giel, C Cai, FR Rodepeter, V Beneš, R Grénman, TE Carey, H Lage, T Stiewe, A Neubauer, JA Werner, C Brendel, R Mandic
Zeitschrift für Krebsforschung und Klinische Onkologie 2014
Importance of ABCC1 for cancer therapy and prognosis
T Kunická, P Souček
Drug Metabolism Reviews 2014
Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways
V Sousa, B Bastos, M Silva, AM Alarcão, L Carvalho
Revista Portuguesa de Pneumologia 2014
Reference Module in Biomedical Sciences
DL Sackett, RB Haynes
2014

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