JOURNAL ARTICLE

Estrogen activation of the mitogen-activated protein kinase is mediated by ER-α36 in ER-positive breast cancer cells

XinTian Zhang, Hao Deng, Zhao-Yi Wang
Journal of Steroid Biochemistry and Molecular Biology 2014, 143: 434-43
24973581
It is well known that there are two estrogen-signaling pathways, genomic estrogen signaling and non-genomic or rapid estrogen signaling. Although both ER-α and ER-β have been suggested to mediate both genomic and non-genomic estrogen signaling, rapid estrogen signaling such as activation of the MAPK/ERK signaling in ER-positive breast cancer MCF7 cells has been controversial. Previously, our laboratory cloned a 36kDa variant of ER-α, ER-α36, that is mainly localized at the plasma membrane and is able to mediate rapid estrogen signaling. In this study, we investigated the function and the underlying mechanisms of ER-α36 in rapid estrogen signaling of ER-positive breast cancer cells. ER-positive breast cancer cells MCF7, T47D and H3396 as well as their variants with different levels of ER-α and ER-α36 expression were used to examine estrogen induction of the MAPK/ERK1/2 signaling. The underlying mechanisms were also studied in these cells with the neutralizing antibodies and chemical inhibitors against different growth factors and their receptors. We found that ER-α36 mediated estrogen induction of the MAPK/ERK phosphorylation in ER-positive breast cancer cells while the full-length ER-α failed to do so. The rapid estrogen signaling mediated by ER-α36 involved a orchestrated action of matrix metalloproteinases (MMPs), heparin-binding epidermal growth factor (HB-EGF), amphiregulin, insulin-like growth factor 1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), HER2/Neu and Src. Our results thus indicated that ER-α36 is the estrogen receptor that mediates estrogen induction of the MAPK/ERK signaling in ER-positive breast cancer cells.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
24973581
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"