Format

Send to

Choose Destination
Cancer Res. 2015 Feb 15;75(4):732-41. doi: 10.1158/0008-5472.CAN-14-0839. Epub 2014 Dec 15.

BRCA2-deficient sarcomatoid mammary tumors exhibit multidrug resistance.

Author information

1
Division of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands. Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
2
Division of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
3
Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, the Netherlands.
4
Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
5
Division of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands. Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. sven.rottenberg@vetsuisse.unibe.ch.

Abstract

Pan- or multidrug resistance is a central problem in clinical oncology. Here, we use a genetically engineered mouse model of BRCA2-associated hereditary breast cancer to study drug resistance to several types of chemotherapy and PARP inhibition. We found that multidrug resistance was strongly associated with an EMT-like sarcomatoid phenotype and high expression of the Abcb1b gene, which encodes the drug efflux transporter P-glycoprotein. Inhibition of P-glycoprotein could partly resensitize sarcomatoid tumors to the PARP inhibitor olaparib, docetaxel, and doxorubicin. We propose that multidrug resistance is a multifactorial process and that mouse models are useful to unravel this.

PMID:
25511378
DOI:
10.1158/0008-5472.CAN-14-0839
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center