The estrogen receptor-interacting protein HPIP increases estrogen-responsive gene expression through activation of MAPK and AKT.
Estrogen receptors (ERalpha and ERbeta) are estrogen-regulated transcription factors that play important roles in the development and progression of breast cancer. The biological function of ERs has been shown to be modulated by ER-interacting proteins. However, the ER-interacting proteins that not only activate MAPK and AKT, two important growth regulatory protein kinases, but also increase growth related estrogen-responsive gene expression remain unknown. Here, we report that hematopoietic PBX-interacting protein (HPIP) interacts both with ERalpha and with ERbeta, and increases ERalpha target gene expression through activation of MAPK and AKT and enhanced ERalpha phosphorylation. ERbeta inhibits ERalpha target gene expression, possibly by competition of ERbeta with ERalpha for binding to HPIP, and by a decrease in available ERalpha for HPIP binding through the interaction of ERbeta with ERalpha. Furthermore, HPIP increases breast cancer cell growth. These data suggest that HPIP may be an important regulator in ER signaling and that the relative ratio of ERbeta to ERalpha may be important for HPIP function.
Wang
Xiaohui
X
Department of Molecular Oncology, Beijing Institute of Biotechnology, Beijing 100850, PR China.
Yang
Zhihong
Z
Zhang
Hao
H
Ding
Lihua
L
Li
Xiru
X
Zhu
Cui
C
Zheng
Yiqiong
Y
Ye
Qinong
Q
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D056970:Co-Repressor Proteins; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D056970:Co-Repressor Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C413449:PBXIP1 protein, human; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D004958:Estradiol; D008156:Luciferases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases