An in vitro model showing adaptation to long-term oestrogen deprivation highlights the clinical potential for targeting kinase pathways in combination with aromatase inhibition

被引：18

作者：

Martin, L-A ^{[1
]}

Ghazoui, Z. ^{[1
]}

Weigel, M. T. ^{[1
]}

Pancholi, Sunil ^{[1
]}

Dunbier, A. ^{[1
]}

Johnston, Stephen ^{[2
]}

Dowsett, M. ^{[1
,2
]}

机构：

[1] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

[2] Royal Marsden Hosp, London SW3 6JJ, England

来源：

STEROIDS | 2011年 / 76卷 / 08期

关键词：

Breast cancer; Oestrogen receptor; Endocrine resistance; Aromatase inhibitor; Kinases; BREAST-CANCER CELLS; RANDOMIZED-TRIAL; TAMOXIFEN; RECEPTOR; HYPERSENSITIVITY; RESISTANCE; GROWTH;

D O I：

10.1016/j.steroids.2011.02.035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aromatase inhibitors (AI) have improved the treatment of oestrogen receptor positive (ER+) breast cancer. Despite the efficacy of these agents over 40% of patients relapse with endocrine resistant disease. Here we describe an in vitro model of acquired resistance to long-term oestrogen deprivation (LTED). The LTED cells retain expression of the ER and appear hypersensitive to oestrogen as a result of altered kinase activity. Furthermore analysis of temporal changes in gene expression during the acquisition of resistance highlight growth factor receptor pathways as key mediators of this adaptive process. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：772 / 776

页数：5