title: Four-and-a-half-LIM protein 1 down-regulates estrogen receptor α activity through repression of AKT phosphorylation in human breast cancer cell.
abstract: The Four-and-a-half LIM protein 1 (FHL-1) is a member of LIM-only protein family. It plays important roles in proliferation and apoptosis regulation of certain hepatocellular carcinoma and human breast cancer. Estrogen receptor α (ERα) is involved in the development and progression of human breast cancer. IGF/PI3K/AKT signaling pathway also plays certain roles in the program and regulation of human breast cancer and ovary cancer. However, the biological function of FHL-1 in regulation of human breast cancer and in the cross-talk of estrogen and IGF signaling pathway remains largely unknown. In this paper, we show that FHL-1 protein interacts with ERα and AKT. FHL-1 represses the translation and transcription of estrogen receptor-responsive genes through down-regulating AKT activation. In addition, FHL-1 is not only an ERα-interacting co-regulation protein, but also decreases the phosphorylation of AKT and ERα. Depression of endogenous FHL-1 by FHL-1 targeted small interfering RNA enhances the expression of these proteins and phosphorylation of AKT and ERα. These data suggest that FHL-1 may regulate ER signaling function through regulation of AKT activation besides the physical and functional interaction with ERα. By establishing a linkage role of the FHL-1 between the estrogen ERα signaling pathway and IGF/PI3K/AKT signaling pathway, this study identifies that FHL-1 proteins may be a useful molecular target for human breast cancer therapy.
authors.affiliation: Tumor Center, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.forename: Pingxun
authors.initials: P
authors.lastname: Yang
authors.forename: Zijian
authors.initials: Z
authors.lastname: Li
authors.forename: Junhao
authors.initials: J
authors.lastname: You
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Xie
authors.forename: Xudong
authors.initials: X
authors.lastname: Gao
authors.forename: Junlan
authors.initials: J
authors.lastname: Yang
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction
chemical_list: D047628:Estrogen Receptor alpha; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; C506487:ESR1 protein, human; C101149:FHL1 protein, human