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Citations to this article

Downregulation of mdr-1 expression by 8-Cl-cAMP in multidrug resistant MCF-7 human breast cancer cells.
S Scala, … , M Tsokos, S E Bates
S Scala, … , M Tsokos, S E Bates
Published August 1, 1995
Citation Information: J Clin Invest. 1995;96(2):1026-1034. https://doi.org/10.1172/JCI118088.
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Research Article

Downregulation of mdr-1 expression by 8-Cl-cAMP in multidrug resistant MCF-7 human breast cancer cells.

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Abstract

8-Cl-cAMP, a site-selective analogue of cAMP, decreased mdr-1 expression in multidrug-resistant human breast cancer cells. A sixfold reduction of mdr-1 mRNA expression by 8-Cl-cAMP began within 8 h of treatment and was associated with a decrease in the synthesis of P-glycoprotein and with an increase in vinblastine accumulation. A reduction in mdr-1 expression after 8-Cl-cAMP treatment was also observed in multidrug-resistant human ovarian cancer cell lines. 8-Cl-cAMP is known to change the ratio between the two regulatory subunits, RI and RII, of protein kinase A (PKA). We observed that RI alpha decreased within 24 h of 8-Cl-cAMP treatment, that RII beta increased after as few as 3 h of treatment, and that PKA catalytic activity remained unchanged during 48 h of 8-Cl-cAMP treatment. The results are consistent with the hypothesis that mdr-1 expression is regulated in part by changes in PKA isoenzyme levels. Although 8-Cl-cAMP has been used to differentiate cells in other model systems, the only differentiating effect that could be detected after 8-Cl-cAMP treatment in the MCF-7TH cells was an increase in cytokeratin expression. Evidence that the reduction of mdr-1 mRNA occurred at the level of gene transcription was obtained by measuring chloramphenicol acetyltransferase (CAT) mRNA in MCF-7TH cells transfected with an mdr-1 promoter-CAT construct prior to 8-Cl-cAMP treatment. Thus, 8-Cl-cAMP is able to downregulate mdr-1 expression and suggests a new approach to reversal of drug resistance in human breast cancer.

Authors

S Scala, A Budillon, Z Zhan, Y S Cho-Chung, J Jefferson, M Tsokos, S E Bates

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Total citations by year

Year: 2021 2016 2015 2014 2010 2009 2008 2006 2004 2002 2001 2000 1999 1998 1997 Total
Citations: 1 1 2 1 1 1 1 1 1 4 2 5 2 6 3 32
Citation information
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Citations to this article in year 2008 (1)

Title and authors Publication Year
Reversal of ABC drug transporter-mediated multidrug resistance in cancer cells: evaluation of current strategies
CP Wu, AM Calcagno, SV Ambudkar
Current molecular pharmacology 2008

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