PDEF promotes luminal differentiation and acts as a survival factor for ER-positive breast cancer cells.
PDEF promotes luminal differentiation and acts as a survival factor for ER-positive breast cancer cells.
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DOI：
10.1016/j.ccr.2013.04.026
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发表时间：
2013-06-10
期刊：
影响因子：
50.3
通讯作者：
Brugge JS
中科院分区：
文献类型：
--
作者：
Buchwalter G;Hickey MM;Cromer A;Selfors LM;Gunawardane RN;Frishman J;Jeselsohn R;Lim E;Chi D;Fu X;Schiff R;Brown M;Brugge JS
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。我们确定前列腺源性ETS因子（PDEF）作为乳腺腔上皮细胞系特异性基因表达的介体，并作为一个因素所需的肿瘤发生在一个子集的乳腺癌。PDEF水平与雌激素受体（ER）阳性的腔型乳腺癌密切相关，并且PDEF转录受ER和GATA 3的负调节。此外，PDEF对于管腔乳腺癌细胞存活是必不可少的，并且是内分泌抵抗模型所必需的。这些结果提供了深入了解这个ETS因素的功能，临床相关的，可能是乳腺癌患者内分泌治疗的治疗价值。ER是乳腺腔肿瘤的决定性转录因子，靶向ER的内分泌药物是乳腺癌的既定护理标准。然而，内在和获得性耐药限制了这种治疗策略的成功，突出了需要确定对管腔肿瘤生长和复发至关重要的其他途径。我们的研究结果提供了证据表明，前列腺源性ETS因子（PDEF）可以驱动基底乳腺上皮细胞的管腔分化，调节管腔肿瘤细胞的存活，并有助于内分泌抵抗。这些发现表明，PDEF表达增加可能在内分泌治疗后的肿瘤复发中发挥作用，并可能成为治疗管腔型乳腺癌患者的临床有用靶点。
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 breast cancer patients treated with endocrine therapy. ER is the defining transcription factor of luminal breast tumors, and endocrine agents that target ER are well-established standards of care in breast cancer. However, intrinsic and acquired resistance limits the success of this therapeutic strategy, highlighting the need to identify additional pathways critical for luminal tumor growth and recurrence. Our findings provide evidence that prostate derived ETS factor (PDEF) can drive luminal differentiation of basal mammary epithelial cells, regulate the survival of luminal tumor cells, and contribute to endocrine resistance. These findings suggest that increased PDEF expression may play a role in tumor recurrence following endocrine therapy and may be a clinically useful target for the treatment of patients with luminal breast cancer.
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影响因子：
6.4
作者：
Ghadersohi, Ali;Odunsi, Kunle;Zhang, Shaozeng;Azrak, Rami G.;Bundy, Brian N.;Manjili, Masoud H.;Li, Fengzhi
通讯作者：
Li, Fengzhi
影响因子：
30.8
作者：
Carroll, Jason S.;Meyer, Clifford A.;Brown, Myles
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影响因子：
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作者：
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通讯作者：
Werb, Zena
DOI：
10.1073/pnas.1115188108
发表时间：
2011-11-22
影响因子：
11.1
作者：
Ariazi, Eric A.;Cunliffe, Heather E.;Jordan, V. Craig
通讯作者：
Jordan, V. Craig
影响因子：
37.3
作者：
Johnson TR;Koul S;Kumar B;Khandrika L;Venezia S;Maroni PD;Meacham RB;Koul HK
通讯作者：
Koul HK