Using the National Cancer Institute Anticancer Drug Screen to Assess the Effect of MRP Expression on Drug Sensitivity Profiles

QUICK SEARCH:

[advanced]

	Author:		Keyword(s):
Year:		Vol:		Page:

This Article

	Full Text
	Full Text (PDF)
	Submit a response
	Alert me when this article is cited
	Alert me when eLetters are posted
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Alvarez, M.
	Articles by Fojo, T.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Alvarez, M.
	Articles by Fojo, T.

Vol. 54, Issue 5, 802-814, November 1998

Using the National Cancer Institute Anticancer Drug Screen to Assess the Effect of MRP Expression on Drug Sensitivity Profiles

M. Alvarez, R. Robey, V. Sandor, K. Nishiyama, Y. Matsumoto, K. Paull, S. Bates, and T. Fojo

Departamento Hematologia-Oncologia, Universidad Catolica de Chile, Santiago, Chile (M.A.), Medicine Branch, Division of Clinical Sciences, National Cancer Institute (R.R., V.S., K.N., Y.M., S.B., T.F.), and Information Technology Branch, Developmental Therapeutics Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 (K.P.)

The MRP gene contributes to one form of multidrug resistance. To identify drugs interacting with MRP, we measured MRP mRNAexpression by quantitative PCR in 60 cell lines of the NationalCancer Institute Anticancer Drug Screen. Expression was detectedin all cell lines (highest in lung carcinomas and central nervoussystem tumors) with a range of 14-fold. A mean graph of MRP mRNAlevels was constructed to determine Pearson correlation coefficients(PCCs) with mean graphs of >40,000 compounds using the COMPAREanalysis. Only 20 compounds had PCCs of $>=$ 0.500. The PCCs for VP-16,doxorubicin, and vincristine were 0.008, 0.13, and 0.257, respectively.Initially, 36 compounds with PCCs of $>=$ 0.428 were analyzed usingtwo MRP-overexpressing cell lines; low levels of cross-resistancewas demonstrated for 23 compounds (1.3-9.4-fold). Twenty-fourcompounds also were available for further studies. Using a fluorescenceactivated cell sorter assay to measure competition of calceinefflux from MRP-overexpressing cells, 10 compounds were foundto increase calcein retention by $>=$ 2-fold. Ten compounds also wereable to reduce ATP-dependent [³H]LTC₄ transport into vesicles from MRP-overexpressing cells.These results contrast with previous studies with MDR-1 in whichhigh correlations were found and confirmed for a large numberof compounds. Although other assays may be more revealing, inthese unselected cell lines, MRP mRNA expression was a poor predictorof drug sensitivity. This raises the possibility that other factors,including conjugating enzymes, glutathione levels, or other transporters,confound the MRPeffect.

This article has been cited by other articles:

C. J. Henrich, R. W. Robey, H. R. Bokesch, S. E. Bates, S. Shukla, S. V. Ambudkar, M. Dean, and J. B. McMahon
New inhibitors of ABCG2 identified by high-throughput screening
Mol. Cancer Ther., December 1, 2007; 6(12): 3271 - 3278.
[Abstract] [Full Text] [PDF]

R. W. Robey, Z. Zhan, R. L. Piekarz, G. L. Kayastha, T. Fojo, and S. E. Bates
Increased MDR1 Expression in Normal and Malignant Peripheral Blood Mononuclear Cells Obtained from Patients Receiving Depsipeptide (FR901228, FK228, NSC630176)
Clin. Cancer Res., March 1, 2006; 12(5): 1547 - 1555.
[Abstract] [Full Text] [PDF]

Z. N. Demidenko, D. Halicka, J. Kunicki, J. A. McCubrey, Z. Darzynkiewicz, and M. V. Blagosklonny
Selective Killing of Adriamycin-Resistant (G2 Checkpoint-Deficient and MRP1-Expressing) Cancer Cells by Docetaxel
Cancer Res., May 15, 2005; 65(10): 4401 - 4407.
[Abstract] [Full Text] [PDF]

K. A. Giuliano
High-Content Profiling of Drug-Drug Interactions: Cellular Targets Involved in the Modulation of Microtubule Drug Action by the Antifungal Ketoconazole
J Biomol Screen, April 1, 2003; 8(2): 125 - 135.
[Abstract] [PDF]

R. Danesi, F. De Braud, S. Fogli, T. M. De Pas, A. Di Paolo, G. Curigliano, and M. Del Tacca
Pharmacogenetics of Anticancer Drug Sensitivity in Non-Small Cell Lung Cancer
Pharmacol. Rev., March 1, 2003; 55(1): 57 - 103.
[Abstract] [Full Text] [PDF]

J. Hong, H. Lu, X. Meng, J.-H. Ryu, Y. Hara, and C. S. Yang
Stability, Cellular Uptake, Biotransformation, and Efflux of Tea Polyphenol (-)-Epigallocatechin-3-Gallate in HT-29 Human Colon Adenocarcinoma Cells
Cancer Res., December 15, 2002; 62(24): 7241 - 7246.
[Abstract] [Full Text] [PDF]

L. J. Yu, J. Matias, D. A. Scudiero, K. M. Hite, A. Monks, E. A. Sausville, and D. J. Waxman
P450 Enzyme Expression Patterns in the NCI Human Tumor Cell Line Panel
Drug Metab. Dispos., March 1, 2001; 29(3): 304 - 312.
[Abstract] [Full Text]

S. D. Mertins, T. G. Myers, M. Hollingshead, D. Dykes, E. Bodde, P. Tsai, C. A. Jefferis, R. Gupta, W. M. Linehan, M. Alley, et al.
Screening for and Identification of Novel Agents Directed at Renal Cell Carcinoma
Clin. Cancer Res., March 1, 2001; 7(3): 620 - 633.
[Abstract] [Full Text]

R. W. Robey, W. Y. Medina-Pérez, K. Nishiyama, T. Lahusen, K. Miyake, T. Litman, A. M. Senderowicz, D. D. Ross, and S. E. Bates
Overexpression of the ATP-binding Cassette Half-Transporter, ABCG2 (MXR/BCRP/ABCP1), in Flavopiridol-resistant Human Breast Cancer Cells
Clin. Cancer Res., January 1, 2001; 7(1): 145 - 152.
[Abstract] [Full Text]

				R. W. Robey, Z. Zhan, R. L. Piekarz, G. L. Kayastha, T. Fojo, and S. E. Bates Increased MDR1 Expression in Normal and Malignant Peripheral Blood Mononuclear Cells Obtained from Patients Receiving Depsipeptide (FR901228, FK228, NSC630176) Clin. Cancer Res., March 1, 2006; 12(5): 1547 - 1555. [Abstract] [Full Text] [PDF]

				Z. N. Demidenko, D. Halicka, J. Kunicki, J. A. McCubrey, Z. Darzynkiewicz, and M. V. Blagosklonny Selective Killing of Adriamycin-Resistant (G2 Checkpoint-Deficient and MRP1-Expressing) Cancer Cells by Docetaxel Cancer Res., May 15, 2005; 65(10): 4401 - 4407. [Abstract] [Full Text] [PDF]

				K. A. Giuliano High-Content Profiling of Drug-Drug Interactions: Cellular Targets Involved in the Modulation of Microtubule Drug Action by the Antifungal Ketoconazole J Biomol Screen, April 1, 2003; 8(2): 125 - 135. [Abstract] [PDF]

				R. Danesi, F. De Braud, S. Fogli, T. M. De Pas, A. Di Paolo, G. Curigliano, and M. Del Tacca Pharmacogenetics of Anticancer Drug Sensitivity in Non-Small Cell Lung Cancer Pharmacol. Rev., March 1, 2003; 55(1): 57 - 103. [Abstract] [Full Text] [PDF]

				J. Hong, H. Lu, X. Meng, J.-H. Ryu, Y. Hara, and C. S. Yang Stability, Cellular Uptake, Biotransformation, and Efflux of Tea Polyphenol (-)-Epigallocatechin-3-Gallate in HT-29 Human Colon Adenocarcinoma Cells Cancer Res., December 15, 2002; 62(24): 7241 - 7246. [Abstract] [Full Text] [PDF]

				L. J. Yu, J. Matias, D. A. Scudiero, K. M. Hite, A. Monks, E. A. Sausville, and D. J. Waxman P450 Enzyme Expression Patterns in the NCI Human Tumor Cell Line Panel Drug Metab. Dispos., March 1, 2001; 29(3): 304 - 312. [Abstract] [Full Text]

				S. D. Mertins, T. G. Myers, M. Hollingshead, D. Dykes, E. Bodde, P. Tsai, C. A. Jefferis, R. Gupta, W. M. Linehan, M. Alley, et al. Screening for and Identification of Novel Agents Directed at Renal Cell Carcinoma Clin. Cancer Res., March 1, 2001; 7(3): 620 - 633. [Abstract] [Full Text]

				R. W. Robey, W. Y. Medina-Pérez, K. Nishiyama, T. Lahusen, K. Miyake, T. Litman, A. M. Senderowicz, D. D. Ross, and S. E. Bates Overexpression of the ATP-binding Cassette Half-Transporter, ABCG2 (MXR/BCRP/ABCP1), in Flavopiridol-resistant Human Breast Cancer Cells Clin. Cancer Res., January 1, 2001; 7(1): 145 - 152. [Abstract] [Full Text]