Das Kakoli, Leong David Tai, Gupta Anurag, Shen Liang, Putti Thomas, Stein Gary S, van Wijnen Andre J, Salto-Tellez Manuel
Department of Pathology, National University of Singapore, Singapore.
Eur J Cancer. 2009 Sep;45(13):2239-48. doi: 10.1016/j.ejca.2009.06.021. Epub 2009 Jul 24.
The runt-related transcription factor, Runx2 may have an oncogenic role in mediating metastatic events in breast cancer, but whether Runx2 has a role in the early phases of breast cancer development is not clear. We examined the expression of Runx2 and its relationship with oestrogen receptor (ER) and progesterone receptor (PR) in breast cancer cell lines and tissues.
Two human breast cancer cell lines, MCF-7 and MDA-MB-231 were transiently transfected with vectors expressing either Runx2 or ER and the levels of both proteins and mRNA were examined by Western blot analysis and quantitative real-time PCR, respectively. Runx2 expression was also examined in tissue microarray sections of 123 breast cancer patients by immunohistochemistry and results were correlated with clinico-pathological characteristics.
Expression of Runx2 and ER was reciprocal in the breast cell culture models and Runx2 suppressed ERbeta but not ERalpha mRNA levels. In contrast, functional expression of Runx2 was evident in the nucleus in 28% of the breast cancer tissues and in both early and late stages of tumour growth. Importantly, Runx2 expression was significantly more frequent in Grade 2 compared to Grade 1 and Grade 3 tumours (48% versus 39% versus 13%) and the expression was significantly associated with ER (p=0.005), PR (p=0.008) expressions in Grade 2 & Grade 3 tumours than Grade 1 tumours.
We propose that Runx2, ER and PR triple positivity in Grades 2 and 3 defines a biological subtype in breast cancer.
矮小相关转录因子Runx2可能在介导乳腺癌转移事件中具有致癌作用，但Runx2在乳腺癌发展早期阶段是否发挥作用尚不清楚。我们检测了Runx2在乳腺癌细胞系和组织中的表达及其与雌激素受体（ER）和孕激素受体（PR）的关系。
用表达Runx2或ER的载体瞬时转染两个人类乳腺癌细胞系MCF-7和MDA-MB-231，分别通过蛋白质印迹分析和定量实时PCR检测两种蛋白质和mRNA的水平。还通过免疫组织化学检测了123例乳腺癌患者组织芯片切片中Runx2的表达，并将结果与临床病理特征相关联。
在乳腺细胞培养模型中，Runx2和ER的表达呈负相关，Runx2抑制ERβ但不抑制ERα的mRNA水平。相比之下，Runx2的功能性表达在28%的乳腺癌组织以及肿瘤生长的早期和晚期的细胞核中均很明显。重要的是，与1级和3级肿瘤相比，Runx2在2级肿瘤中的表达明显更频繁（48%对39%对13%），并且在2级和3级肿瘤中，Runx2的表达与ER（p=0.005）、PR（p=0.008）的表达显著相关，而在1级肿瘤中则不然。
我们提出，2级和3级肿瘤中Runx2、ER和PR三联阳性定义了乳腺癌的一种生物学亚型。
