ELL-associated factor 1 is a transcription elongation factor that shares significant homology and functional similarity to the androgen-responsive prostate tumor suppressor ELL-associated factor 2. EAF2 is frequently down-regulated in advanced prostate cancer and Eaf2 deletion in the mouse induced the development of murine prostatic intraepithelial neoplasia. Here we show that similar to EAF2, EAF1 is frequently down-regulated in advanced prostate cancer. Co-downregulation of EAF1 and EAF2 occurred in 40% of clinical specimens with Gleason score >7. We developed and characterized a murine model of prostate-epithelial specific deletion of Eaf1 in the prostate and crossed it with our previously generated mouse with conventional deletion of Eaf2. The prostates of Eaf1 deletion mice displayed murine prostatic intraepithelial neoplasia lesions with increased proliferation and inflammation. Combined deletion of Eaf1 and Eaf2 in the murine model induced an increased incidence in mPIN lesions characterized by increased proliferation and CD3+ T cells and CD19+ B cells infiltration compared to individual deletion of either Eaf1 or Eaf2 in the murine prostate. These results suggest that EAF1 may play a tumor suppressive role in the prostate. Cooperation between EAF1 and EAF2 may be important for prostate maintaining prostate epithelial homeostasis, and concurrent loss of these two tumor suppressors may promote prostate tumorigenesis and progression.

中文翻译：

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Eaf1的条件删除诱导小鼠前列腺上皮内瘤变。

ELL相关因子1是一种转录延伸因子，与雄激素反应性前列腺肿瘤抑制因子ELL相关因子2具有显着的同源性和功能相似性。EAF2在晚期前列腺癌中经常被下调，小鼠中的Eaf2缺失会诱导其发育。鼠前列腺上皮内瘤变。在这里，我们显示与EAF2类似，EAF1在晚期前列腺癌中经常被下调。EAF1和EAF2的共下调发生在40％的Gleason评分> 7的临床标本中。我们开发并表征了小鼠前列腺中Eaf1特异性上皮特异性缺失的小鼠模型，并将其与我们先前产生的具有Eaf2常规缺失的小鼠杂交。Eaf1缺失小鼠的前列腺表现出鼠前列腺上皮内瘤形成病变，增殖和炎症增加。与在鼠前列腺中单独缺失Eaf1或Eaf2相比，在鼠模型中Eaf1和Eaf2的联合缺失导致mPIN损伤的发生率增加，其特征是增殖和CD3 + T细胞和CD19 + B细胞浸润​​增加。这些结果表明，EAF1可能在前列腺中发挥肿瘤抑制作用。EAF1和EAF2之间的合作对于前列腺维持前列腺上皮体内稳态可能很重要，同时丢失这两种肿瘤抑制剂可能会促进前列腺癌的发生和发展。与在鼠前列腺中单独缺失Eaf1或Eaf2相比，在鼠模型中Eaf1和Eaf2的联合缺失导致mPIN损伤的发生率增加，其特征是增殖和CD3 + T细胞和CD19 + B细胞浸润​​增加。这些结果表明，EAF1可能在前列腺中发挥肿瘤抑制作用。EAF1和EAF2之间的合作对于前列腺维持前列腺上皮体内稳态可能很重要，同时丢失这两种肿瘤抑制剂可能会促进前列腺癌的发生和发展。与在鼠前列腺中单独缺失Eaf1或Eaf2相比，在鼠模型中Eaf1和Eaf2的联合缺失导致mPIN损伤的发生率增加，其特征是增殖和CD3 + T细胞和CD19 + B细胞浸润​​增加。这些结果表明，EAF1可能在前列腺中发挥肿瘤抑制作用。EAF1和EAF2之间的合作对于前列腺维持前列腺上皮体内稳态可能很重要，同时丢失这两种肿瘤抑制剂可能会促进前列腺癌的发生和发展。