RUNX3 acts as a tumor suppressor in breast cancer by targeting estrogen receptor α

被引：0
作者：
B Huang
Z Qu
C W Ong
Y-H N Tsang
G Xiao
D Shapiro
M Salto-Tellez
K Ito
Y Ito
L-F Chen
机构：
[1] University of Illinois at Urbana-Champaign,Department of Biochemistry
[2] University of Pittsburgh Cancer Institute,Department of Pathology
[3] University of Pittsburgh Medical Center,undefined
[4] National University of Singapore,undefined
[5] Cancer Science Institute of Singapore,undefined
[6] National University of Singapore,undefined
[7] Institute of Molecular and Cell Biology,undefined
[8] Graduate School of Biomedical Sciences,undefined
[9] Nagasaki University,undefined
[10] College of Medicine,undefined
[11] University of Illinois at Urbana-Champaign,undefined
来源：
Oncogene | 2012年 / 31卷
关键词：
breast cancer; degradation; ERα; RUNX3; tumor suppressor;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Transcription factor RUNX3 is inactivated in a number of malignancies, including breast cancer, and is suggested to function as a tumor suppressor. How RUNX3 functions as a tumor suppressor in breast cancer remains undefined. Here, we show that about 20% of female Runx3+/− mice spontaneously developed ductal carcinoma at an average age of 14.5 months. Additionally, RUNX3 inhibits the estrogen-dependent proliferation and transformation potential of ERα-positive MCF-7 breast cancer cells in liquid culture and in soft agar and suppresses the tumorigenicity of MCF-7 cells in severe combined immunodeficiency mice. Furthermore, RUNX3 inhibits ERα-dependent transactivation by reducing the stability of ERα. Consistent with its ability to regulate the levels of ERα, expression of RUNX3 inversely correlates with the expression of ERα in breast cancer cell lines, human breast cancer tissues and Runx3+/− mouse mammary tumors. By destabilizing ERα, RUNX3 acts as a novel tumor suppressor in breast cancer.
引用
收藏
页码：527 / 534
页数：7
相关论文
共 130 条
  • [1] Anderson E(2002)The role of oestrogen and progesterone receptors in human mammary development and tumorigenesis Breast Cancer Res 4 197-201
  • [2] Cheskis BJ(2007)Signaling by estrogens J Cell Physiol 213 610-617
  • [3] Greger JG(2005)RUNX3 suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1) expression in cooperation with transforming growth factor {beta}-activated SMAD Mol Cell Biol 25 8097-8107
  • [4] Nagpal S(2007)Differential regulation of estrogen receptor alpha turnover and transactivation by Mdm2 and stress-inducing agents Cancer Res 67 5513-5521
  • [5] Freedman LP(1996)Identification of amino acids in the hormone binding domain of the human estrogen receptor important in estrogen binding J Biol Chem 271 20053-20059
  • [6] Chi XZ(2004)Inhibiting proteasomal proteolysis sustains estrogen receptor-alpha activation Mol Endocrinol 18 2603-2615
  • [7] Yang JO(2005)Deregulated estrogen receptor alpha expression in mammary epithelial cells of transgenic mice results in the development of ductal carcinoma Cancer Res 65 681-685
  • [8] Lee KY(2009)Runx3 expression in gastrointestinal tract epithelium: resolving the controversy Oncogene 28 1379-1384
  • [9] Ito K(2008)RUNX3 attenuates beta-catenin/T cell factors in intestinal tumorigenesis Cancer Cell 14 226-237
  • [10] Sakakura C(2004)Oncogenic potential of the RUNX gene family: ‘overview’ Oncogene 23 4198-4208
12345678910