期刊
CLINICAL CANCER RESEARCH
卷 14, 期 21, 页码 6944-6954出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-08-0408
关键词
-
类别
资金
- Terry Fox Foundation
- National Cancer Institute of Canada
- Canadian Breast Cancer Research Alliance
Purpose: Insulin-like growth factor (IGF) binding proteins (IGFBP) modulate interactions of IGF ligands with the IGF-1 receptor. The role of IGFBPs, and specifically IGFBP-2, in breast cancer progression has been poorly defined. This study assesses the effect of IGFBP-2 on the behavior of human breast cancer using clinical specimens as well as in vitro and in vivo experimental systems. Experimental Design: 4,181 primary invasive breast cancers and 120 benign breast tissue samples were identified for tumor tissue microarray construction and immunostained with IGFBP-2 antibody. Estrogen receptor-negative MDA-MB-231 cells constitutively overexpressing IGFBP-2 (MDA-MB-231BP-2) were created to assess the effect of IGFBP-2 gain-of-function. MDA-MB-468 cells, naturally expressing IGFBP-2, were used to determine the effect of IGFBP-2 loss-of-function using OGX-225, an antisense oligonucleotide drug candidate. Results: IGFBP-2 expression was significantly higher in breast cancer tissue compared with benign breast tissue. MDA-MB-231BP-2 cells grew more rapidly and were more resistant to paclitaxel both in vitro and in vivo compared with parental cells. OGX-225 decreased IGFBP-2 expression and attenuated the associated aggressive phenotype of MDA-MB-231BP-2 cells both in vitro and in vivo. Furthermore, OGX-225 inhibited the in vitro and in vivo growth of MDA-MB-468 cells. Conclusions: This study provides evidence that IGFBP-2 expression is associated with breast cancer. Novel therapeutics targeting IGFBP-2, such as OGX-225, merit further evaluation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据