FHL1 interacts with oestrogen receptors and regulates breast cancer cell growth.
Four and a half LIM protein 1 (FHL1) belongs to the Lin-1, Isl-1 and Mec-3 (LIM)-only protein family and plays important roles in muscle growth and carcinogenesis. However, the biological function of FHL1 remains largely unknown. Here, we show that FHL1 physically and functionally interacted with oestrogen receptors (ERs), which are involved in breast cancer development and progression. FHL1 bound specifically to the activation function-1 domain of ER. Physical interaction of FHL1 and ER is required for FHL1 repression of oestrogen-responsive gene transcription. FHL1 affected recruitment of ER to an oestrogen-responsive promoter and ER binding to an oestrogen-responsive element. Overexpression of FHL1 in breast cancer cells decreased expression of oestrogen-responsive proteins, whereas knockdown of endogenous FHL1 with FHL1 small interfering RNA increased the expression of these proteins. Further analysis of 46 breast cancer samples showed that FHL1 expression negatively associated with oestrogen-responsive gene expression in breast cancer cells. FHL1 inhibited anchorage-dependent and -independent breast cancer cell growth. These results suggest that FHL1 may play an important role in ER signalling as well as breast cancer cell growth regulation.
Department of Molecular Oncology, Beijing Institute of Biotechnology, Beijing, China.
Lihua
L
Ding
Chang
C
Niu
Yiqiong
Y
Zheng
Zhihong
Z
Xiong
Yufei
Y
Liu
Jing
J
Lin
Huiwei
H
Sun
Ke
K
Huang
Wen
W
Yang
Xiru
X
Li
Qinong
Q
Ye
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D060588:LIM Domain Proteins; D008875:Middle Aged; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering