Role of AIB1 for tamoxifen resistance in estrogen receptor-positive breast cancer cells.
OBJECTIVE
The p160 nuclear receptor coactivator, AIB1 (amplified in breast cancer 1), is frequently overexpressed in human breast cancer and has been shown to be associated with tamoxifen resistance. The present study aimed to investigate the role of AIB1 in tamoxifen resistance of breast cancer cells.


METHODS
We reconstructed the RNA interference expression vector, pGenesil-1-U6, specially targeting AIB1 mRNA, and it was stably transfected into the human breast cancer cell line BT474. Cell proliferation and cell cycle distribution were assessed in the cells transfected with scramble control shRNA (BT474/shControl) and AIB1 shRNA (BT474/shAIB1) to explore the possible functions of AIB1 in breast cancer progression. The expression of AIB1, ERalpha, HER2 and pS2 was analyzed in the presence of 17beta-estradiol or 4-hydroxytamoxifen (Tam) by Western blot analysis.


RESULTS
Compared with the parental BT474 and the BT474/shControl cells, the levels of AIB1 mRNA and protein were significantly reduced in BT474/shAIB1 cells. A knockdown of AIB1 levels restored the inhibitory effect of tamoxifen on cell proliferation.


CONCLUSIONS
Tam behaves like an estrogen agonist in ER-positive breast cancer cells that express high levels of AIB1 and HER2, resulting in de novo resistance. Knockdown of AIB1 can eliminate this cross talk and restore the antitumor effects of tamoxifen.
Su
Qingbo
Q
Department of General Surgery, Qilu Hospital, Shandong University, Jinan, PR China.
Hu
Sanyuan
S
Gao
Haidong
H
Ma
Rong
R
Yang
Qifeng
Q
Pan
Zhenhua
Z
Wang
Tiantian
T
Li
Feng
F
D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D056921:Nuclear Receptor Coactivator 3; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; C508861:PSEN2 protein, human; D053766:Presenilin-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3