Characterization and prognostic value of LXR splice variants in triple-negative breast cancer

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J. Bernadette Moore¹  Priscilia Lianto¹  James L. Thorne¹  Thomas A. Hughes²  Samantha A. Hutchinson³ 

[1] School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK;School of Medicine, University of Leeds, Leeds LS9 7TF, UK;The Institute of Cancer Research, Division of Cancer Therapeutics, London SM2 5NG, UK;

关键词: Molecular biology;    Molecular mechanism of gene regulation;    Cancer systems biology;    Cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Activity of liver x receptor (LXR), the homeostatic regulator of cholesterol metabolism, is elevated in triple-negative breast cancer (BCa) relative to other BCa subtypes, driving drug resistance and metastatic gene signatures. The loci encoding LXRα and LXRβ produce multiple alternatively spliced proteins, but the true range of variants and their relevance to cancer remain poorly defined. Here, we report seven LXR splice variants, three of which have not previously been reported and five that were prognostic for disease-free survival. Expression of full-length LXRα splice variants was associated with poor prognosis, consistent with a role as an oncogenic driver of triple-negative tumor pathophysiology. Contrary to this was the observation that high expression of truncated LXRα splice variants or any LXRβ splice variant was associated with longer survival. These findings indicate that LXR isoform abundance is an important aspect of understanding the link between dysregulated cholesterol metabolism and cancer pathophysiology.

【 授权许可】

Unknown