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Estrogen Regulation of Jun and Fos in MCF‐7 Cells
Author(s) -
Geck Renee,
Magill Jessica N.,
Schmitt John M.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1031.14
Subject(s) - mapk/erk pathway , phosphorylation , chemistry , kinase , microbiology and biotechnology , activator (genetics) , protein kinase a , c jun , transcription (linguistics) , mcf 7 , transcription factor , biology , cancer cell , gene , biochemistry , cancer , human breast , philosophy , genetics , linguistics
C‐Fos and c‐Jun are transcription factors that form the dimer Activator Protein 1 (AP‐1) and bind DNA to initiate transcription. C‐Fos, c‐Jun are targets of the E xtracellular Signal‐ R egulated K inase (ERK) in multiple cell types, including MCF‐7 breast cancer cells. The hormone estrogen (E2) can increase intracellular calcium levels which activates calcium/calmodulin‐dependent kinase (CaM Kinase) proteins, which control ERK and gene transcription. Our goal was to evaluate the ability of E2 to activate c‐Fos and c‐Jun and induce their dimerization, via CaM KK and ERK, in MCF‐7 cells. Interestingly, E2 stimulation of MCF‐7 cells triggered phosphorylation of c‐Jun and c‐Fos an effect that was blocked with STO‐609 and U0126, which target CaM KK and ERK, respectively. siRNA inhibition of CaM KK and ERK blocked E2‐stimulated c‐Jun and c‐Fos phosphorylation. Additionally, E2 triggered AP‐1 directed luciferase activity in MCF‐7 cells that was blocked by inhibiting either CaM KK or ERK with siRNA. In summary, our data suggests that E2 utilizes both CaM KK and ERK to phosphorylate c‐Jun and c‐Fos and regulate their transcriptional activity in breast cancer cells.