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

The Journal of Clinical Investigation
S ScalaS E Bates

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...Continue Reading

References

May 6, 1992·Journal of the National Cancer Institute·C E HerzogA T Fojo
May 30, 1991·International Journal of Cancer. Journal International Du Cancer·F GuadagniJ W Greiner
Jan 16, 1991·Journal of the National Cancer Institute·P VerrelleJ Chassagne
Jan 15, 1990·Biochemical and Biophysical Research Communications·S TanakaM M Gottesman
Sep 1, 1990·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·C Cordon-CardoM R Melamed
Mar 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·G TortoraY S Cho-Chung
Jan 1, 1991·Cancer Chemotherapy and Pharmacology·Y TakemuraT Ohnuma
Oct 1, 1990·International Journal of Radiation Oncology, Biology, Physics·E Baral, G Auer
Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A T FojoI Pastan
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F ThiebautM C Willingham
Jul 1, 1989·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·P S Rudland, C M Hughes
Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·G TortoraY S Cho-Chung
Nov 2, 1988·Journal of the National Cancer Institute·R K Burt, S S Thorgeirsson
Dec 1, 1988·Molecular Endocrinology·M SacedaM B Martin
May 28, 1987·The New England Journal of Medicine·I Pastan, M Gottesman
Apr 1, 1981·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·S M HsuH Fanger
Jan 1, 1995·Cancer Chemotherapy and Pharmacology·S E BatesL J Elwood

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Citations

Aug 14, 1999·International Journal of Cancer. Journal International Du Cancer·A M ParissentiS Glück
Jan 1, 1997·Pathology Oncology Research : POR·Adorján Aszalós, Sándor Eckhardt
Sep 29, 2000·Pharmacology & Therapeutics·F SchwedeB Jastorff
Jun 12, 1998·Pharmacology & Therapeutics·M E CvijicK V Chin
Nov 13, 2008·Cytotechnology·K W Scotto, D A Egan
Nov 13, 2008·Cytotechnology·M G RumsbyJ R Warr
Jul 18, 2002·Annals of the New York Academy of Sciences·Giampaolo Tortora, Fortunato Ciardiello
Jul 1, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ziyuan WangPeihao Yin
Dec 20, 2005·Seminars in Oncology·Antonio Tito Fojo, Michael Menefee
Jul 18, 2002·Annals of the New York Academy of Sciences·W R Miller
Jan 18, 2006·The Journal of Pharmacology and Experimental Therapeutics·Christina ZiemannKaren I Hirsch-Ernst
Jul 17, 1997·International Journal of Cancer. Journal International Du Cancer·M E Cvijic, K V Chin
Sep 21, 2000·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G Tortora, F Ciardiello

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