Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells.

Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells. Research Abstract Details 

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Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells. Abstract Text:

Hong Liu,Dong Cheng,Alyssa K Weichel,Clodia Osipo,Laura K Wing,Bin Chen,Teresa E Louis,V Craig Jordan,

The selective ER downregulator, fulvestrant, is currently approved as a second line endocrine therapy after onset of resistance to prior antiestrogen therapy in postmenopausal breast cancer patients. Resistance to antihormonal therapies is common and, therefore, we anticipate that fulvestrant-resistance will occur as well. The current study was undertaken to investigate the underlying molecular changes after fulvestrant-resistance and find new therapeutic targets and agents for fulvestrant-resistant breast cancer cells. We developed a unique fulvestrant-resistant cell line (MCF-7/F), derived from MCF-7 estrogen receptor alpha (ERalpha)-positive human breast cancer cells, by culturing them in 1 microM fulvestrant containing medium for approximately 18 months. MCF-7/F cells became irreversibly ERalpha negative as withdrawal of fulvestrant did not alter the ERalpha-negative phenotype, determined by real-time PCR, Western blot analysis, and ERE-luciferase transfection assays. MCF-7/F cells grew in a hormone-independent manner. Interestingly, MCF-7/F cells overexpressed both epidermal growth factor receptor (EGFR) and breast cancer resistant protein (BCRP). Gefitinib, a specific EGFR tyrosine kinase inhibitor, preferentially inhibited the growth of MCF-7/F cells relative to MCF-7 cells by inhibiting both MAPK44/42 and Akt phosphorylation. MCF-7/F cells became less sensitive to chemotherapeutic agents such as mitoxantrone. Moreover, fumitremorgin C, a specific BCRP inhibitor, significantly increased the efficacy of mitoxantrone in MCF-7/F cells. Gefitinib increased the inhibitory effect of mitoxantrone on cell growth. Similarly, fumitremorgin C increased the inhibitory effect of gefitinib on cell growth, suggesting that there is a bidirectional crosstalk between EGFR and BCRP. More importantly, these results provide a molecular basis for using gefitinib, BCRP inhibitors, and chemotherapeutic agents as combination therapy approaches in fulvestrant-resistant breast cancer.

Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells. Publishing Authors By Initials

H Liu,D Cheng,AK Weichel,C Osipo,LK Wing,B Chen,TE Louis,VC Jordan,

For similar heterocyclic compounds: heterocyclic compounds, 2-ring: quinazolines research abstracts see: heterocyclic compounds: heterocyclic compounds, 2-ring: quinazolines research

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Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: International journal of oncology

VOLUME: 29

Page Numbers: 1237-46

Journal Abbreviation: Int. J. Oncol.

ISSN: 1019-6439

DAY: 3

MONTH: Nov

YEAR: 2006

Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells. Information

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LANGUAGE: eng

NlmUniqueID: 9306042

Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells. Keywords Mesh Terms:

KEYWORDS: Quinazolines

MESH TERMS: therapeutic use

Chemical & Substance for Abstract: Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells. Information

Substance Name: Proto-Oncogene Proteins c-akt

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells.

AFFILIATION: Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.

Country: Greece

AGENCY: United States NCI

GRANT: CA 89018

ACRONYM: CA

MEDLINETA: Int J Oncol

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