Zhong Mingming, Pascal Laura E, Cheng Erdong, Masoodi Khalid Z, Chen Wei, Green Anthony, Cross Brian W, Parrinello Erica, Rigatti Lora H, Wang Zhou
Department of Urology, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA.
Transcriptomics Lab, Division of Plant Biotechnology SKUAST-K, Shalimar, Srinagar, J&K, India.
Am J Clin Exp Urol. 2018 Dec 20;6(6):234-244. eCollection 2018.
Elongation factor for RNA polymerase II 2 (ELL2) and ELL-associated factor 2 (EAF2) are two functionally related androgen responsive gene-encoded proteins with prostate tumor suppressor characteristics. EAF2 and ELL2 have both been shown to be down-regulated in advanced prostate cancer, and mice with either or deficiency developed murine prostatic intraepithelial neoplasia (mPIN), increased cellular proliferation and increased vascularity. Functional studies have revealed that EAF2 and ELL2 can bind to each other and have similar roles in regulating cell proliferation, angiogenesis and prostate homeostasis. Here, cell line experiments showed that knockdown of EAF2 or ELL2 induced an increase in proliferation and migration in C4-2 and 22Rv1 prostate cancer cells. Concurrent knockdown of EAF2 and ELL2 increased proliferation and migration similarly to the loss of EAF2 or ELL2 alone. Mice with homozygous deletion of or heterozygous deletion of developed mPIN lesions characterized by increased epithelial proliferation, intraductal microvessel density, and infiltrating intraductal CD3-positive T-cells compared to wild-type controls. Mice with combined heterozygous deletion of and developed mPIN lesions that were similar to those observed in mice with deficiency in Eaf2 or Ell2 alone. These results suggest that EAF2 and ELL2 have similar functions and are likely to require each other in their regulation of prostate epithelial cell proliferation and migration in prostate cancer cells as well as their tumor suppressive properties in the murine prostate.
RNA聚合酶II 2延伸因子（ELL2）和ELL相关因子2（EAF2）是两种功能相关的雄激素反应性基因编码蛋白，具有前列腺肿瘤抑制特性。EAF2和ELL2在晚期前列腺癌中均被证明表达下调，Eaf2或Ell2基因敲除的小鼠会发生小鼠前列腺上皮内瘤变（mPIN），细胞增殖增加且血管生成增多。功能研究表明，EAF2和ELL2可以相互结合，在调节细胞增殖、血管生成和前列腺内环境稳定方面具有相似作用。在此，细胞系实验表明，敲低EAF2或ELL2会导致C4-2和22Rv1前列腺癌细胞的增殖和迁移增加。同时敲低EAF2和ELL2会使增殖和迁移增加，与单独敲低EAF2或ELL2的情况相似。与野生型对照相比，Eaf2纯合缺失或Ell2杂合缺失的小鼠发生了mPIN病变，其特征为上皮增殖增加、导管内微血管密度增加以及导管内CD3阳性T细胞浸润。Eaf2和Ell2联合杂合缺失的小鼠发生的mPIN病变与单独Eaf2或Ell2基因敲除小鼠中观察到的病变相似。这些结果表明，EAF2和ELL2具有相似功能，在调节前列腺癌细胞中前列腺上皮细胞增殖和迁移以及在小鼠前列腺中的肿瘤抑制特性方面可能相互依赖。
