A new mechanism of drug resistance in breast cancer cells: Fatty acid synthase overexpression-mediated palmitate overproduction

Hailan Liu, Yang Liu, Jian-Ting Zhang

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Multidrug resistance is a major problem in successful cancer chemotherapy. Various mechanisms of resistance, such as ABC transporter-mediated drug efflux, have been discovered using established model cancer cell lines. While characterizing a drug-resistant breast cancer cell line, MCF7/AdVp3000, we found that fatty acid synthase (FASN) is overexpressed. In this study, we showed that ectopic overexpression of FASN indeed causes drug resistance and that reducing the FASN expression increased the drug sensitivity in breast cancer cell lines MCF7 and MDA-MB-468 but not in the normal mammary epithelial cell line MCF10A1. Use of FASN inhibitor, Orlistat, at low concentrations also sensitized cells with FASN overexpression to anticancer drugs. The FASN-mediated drug resistance appears to be due to a decrease in drug-induced apoptosis from an overproduction of palmitic acid by FASN. Together with previous findings of FASN as a poor prognosis marker for breast cancer patients, our results suggest that FASN overexpression is a new mechanism of drug resistance and may be an ideal target for chemosensitization in breast cancer chemotherapy.

Original languageEnglish
Pages (from-to)263-270
Number of pages8
JournalMolecular Cancer Therapeutics
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2008

Fingerprint

Fatty Acid Synthases
Palmitates
Drug Resistance
Breast Neoplasms
Cell Line
Pharmaceutical Preparations
Drug Therapy
ATP-Binding Cassette Transporters
Palmitic Acid
Multiple Drug Resistance
Neoplasms
Breast
Epithelial Cells
Apoptosis

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

A new mechanism of drug resistance in breast cancer cells : Fatty acid synthase overexpression-mediated palmitate overproduction. / Liu, Hailan; Liu, Yang; Zhang, Jian-Ting.

In: Molecular Cancer Therapeutics, Vol. 7, No. 2, 01.02.2008, p. 263-270.

Research output: Contribution to journalArticle

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