Division of Molecular and Cellular Oncology, Department of Medical Oncology, and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
Cancer Cell. 2013 Jun 10;23(6):753-67. doi: 10.1016/j.ccr.2013.04.026.
Breast cancer is a heterogeneous disease and can be classified based on gene expression profiles that reflect distinct epithelial subtypes. We identify prostate-derived ETS factor (PDEF) as a mediator of mammary luminal epithelial lineage-specific gene expression and as a factor required for tumorigenesis in a subset of breast cancers. PDEF levels strongly correlate with estrogen receptor (ER)-positive luminal breast cancer, and PDEF transcription is inversely regulated by ER and GATA3. Furthermore, PDEF is essential for luminal breast cancer cell survival and is required in models of endocrine resistance. These results offer insights into the function of this ETS factor that are clinically relevant and may be of therapeutic value for patients with breast cancer treated with endocrine therapy.
乳腺癌是一种异质性疾病，可以根据反映不同上皮亚型的基因表达谱进行分类。我们发现前列腺衍生的 ETS 因子（PDEF）是乳腺腔上皮谱系特异性基因表达的介质，也是一部分乳腺癌发生肿瘤的必需因素。PDEF 水平与雌激素受体（ER）阳性的乳腺腔癌强烈相关，PDEF 转录受 ER 和 GATA3 的反向调节。此外，PDEF 对乳腺腔癌细胞的存活是必需的，并且在激素抵抗模型中也是必需的。这些结果提供了对该 ETS 因子的功能的深入了解，这些发现与临床相关，对于接受内分泌治疗的乳腺癌患者可能具有治疗价值。
