Metformin affects alternative splicing of the estrogen receptor alpha gene in breast cancer cells
Yoshihiro Harada1,
Tomoko Tanaka2, Yuriko Hamaguchi2,Yuta Horita1,
Masayoshi Mori1, Yusuke Murata1, Munechika Enjoji1,
Kenji Ohe1,*
1. Department of
Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University,
8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
2.Department
of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka
University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
ABSTRACT
Metformin ameliorates insulin resistance and reported to have prophylactic potential in breast cancer.
The estrogen receptor-alpha gene is known to be alternatively spliced to the
ER?46 isoform with decreased
expression in tamoxifen-resistant breast cancer cells. We show here that
metformin had a differential effect on its
alternative splicing in MCF-7 and its tamoxifen-resistant derivative, TAMR1
cells. Metformin altered the tamoxifen-induced expression of ER?46 and treatment of cell-transplanted nude
mice showed decreased tumor weight only in TAMR1 cell tumors. This is the first
report to show metformin specifically involved in alternative splicing of genes in breast cancer cells.
Keywords: Estrogen receptor-alpha (ER?), estrogen, tamoxifen, metformin