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Oncology. 2008;75(3-4):159-68. doi: 10.1159/000159267. Epub 2008 Oct 1.

Role of AIB1 for tamoxifen resistance in estrogen receptor-positive breast cancer cells.

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  • 1Department of General Surgery, Qilu Hospital, Shandong University, Jinan, PR China.

Abstract

OBJECTIVES:

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.

Copyright 2008 S. Karger AG, Basel.

[PubMed - indexed for MEDLINE]
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