Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Oncogene. 2012 Jan 26;31(4):527-34. doi: 10.1038/onc.2011.252. Epub 2011 Jun 27.
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.
转录因子 RUNX3 在多种恶性肿瘤中失活，包括乳腺癌，并被认为是一种肿瘤抑制因子。然而，RUNX3 在乳腺癌中作为肿瘤抑制因子的功能仍未被定义。在这里，我们发现约 20%的雌性 Runx3(+/-)小鼠在平均 14.5 个月的年龄时自发发展为导管癌。此外，RUNX3 抑制了 ERα 阳性 MCF-7 乳腺癌细胞在液体培养和软琼脂中的雌激素依赖性增殖和转化潜能，并抑制了 MCF-7 细胞在严重联合免疫缺陷小鼠中的致瘤性。此外，RUNX3 通过降低 ERα 的稳定性来抑制 ERα 依赖性的转录激活。与它调节 ERα 水平的能力一致，RUNX3 的表达与乳腺癌细胞系、人乳腺癌组织和 Runx3(+/-)小鼠乳腺肿瘤中的 ERα 表达呈负相关。通过使 ERα 不稳定，RUNX3 作为一种新型的肿瘤抑制因子在乳腺癌中发挥作用。
