Pharmaceutical Research

, Volume 28, Issue 12, pp 3091–3100

Regulation of miR-19 to Breast Cancer Chemoresistance Through Targeting PTEN

Research Paper

ABSTRACT

Purpose

To explore whether miR-19 is involved in the regulation of multidrug resistance (MDR), one of the main causes of breast cancer mortality, and modulates sensitivity of tumor cells to chemotherapeutic agents.

Methods

We analyzed miRNA expression levels in three MDR cell lines in comparison with their parent cell line, MCF-7, using a miRNA microarray. We investigated whether inhibitor of miR-19 sensitized MDR cells to chemotherapeutic agents in vitro and in vivo.

Results

MiR-19 was overexpressed in all three MDR cell lines compared to their parental cell line, MCF-7. Expression levels of miR-19 in MDR cells were inversely consistent with those of PTEN. Inhibitor of miR-19a restored sensitivity of MDR cells to cytotoxic agents; administration of LNA-antimiR-19a, a chemo-modified miR-19a inhibitor, sensitized MDR cells to chemotherapeutic agents in vivo.

Conclusion

Our findings demonstrate, for the first time, involvement of miR-19 in multidrug resistance through modulation of PTEN and suggest that miR-19 may be a potential target for preventing and reversing MDR in tumor cells.

KEY WORDS

breast cancer microRNA multidrug resistance PTEN 

ABBREVIATIONS

BCRP

breast cancer resistance protein

LNA

locked nucleic acid

MDR

multidrug resistance

MDR-1

multidrug resistance 1

miRNA

microRNA

MRP-1

multidrug resistance-associated protein 1

PTEN

phosphatase and tensin homolog

RT-PCR

reverse transcription polymerase chain reaction.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Radiology and Imaging SciencesEmory UniversityAtlantaUSA
  2. 2.Winship Cancer InstituteEmory UniversityAtlantaUSA
  3. 3.Yerkes Microarray Core, Yerkes National Primate Research Center Emory UniversityAtlantaUSA

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