title: Inhibition of FOSL1 overexpression in antiestrogen-resistant MCF-7 cells decreases cell growth and increases vacuolization and cell death.
abstract: Elevated activator protein-1 (AP-1) activity in breast cancer cells has been linked to Tamoxifen (TAM) resistance. Fos-like antigen-1 (FOSL1) is a member of the AP-1 transcription factor and is overexpressed in a variety of human cancers including breast tumors. We have previously established an estrogen-independent and antiestrogen Toremifene (TOR)-resistant subline of MCF-7 breast cancer cells. In these cells, the expression of FOSL1 is upregulated when compared to the parental cells. In the present study, partial inhibition of FOSL1 expression in these cells by small interfering RNA resulted in a marked decrease of cell growth. The inhibition of cell growth paralleled with changes in cell morphology such as increased formation of vacuoles followed by an increase in the number of dead cells. The inhibition of FOSL1 expression in these cells also restored sensitivity to TOR. Our results suggest that chemotherapy targeting overexpression of FOSL1 could be a potent strategy for treating endocrine resistant breast cancers.
authors.affiliation: Department of Cell Biology, Medical School, FIN-33014, University of Tampere, Finland. pasi.pennanen@uta.fi
authors.forename: Pasi T
authors.initials: PT
authors.lastname: Pennanen
authors.forename: Nanna S
authors.initials: NS
authors.lastname: Sarvilinna
authors.forename: Tarja
authors.initials: T
authors.lastname: Toimela
authors.forename: Timo J
authors.initials: TJ
authors.lastname: Ylikomi
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D006801:Humans; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017312:Toremifene / Q000494:pharmacology; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism; D000099169:Fos-Related Antigen 1
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D016760:Proto-Oncogene Proteins c-fos; D017312:Toremifene; D000099169:Fos-Related Antigen 1