Jeon Hyun Yong, Choi Murim, Howlett Eric L, Vozhilla Nikollaq, Yoo Byoung Kwon, Lloyd Joyce A, Sarkar Devanand, Lee Seok-Geun, Fisher Paul B
Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Gene Expr Patterns. 2010 Oct-Dec;10(7-8):361-7. doi: 10.1016/j.gep.2010.08.004. Epub 2010 Aug 22.
Expression of astrocyte elevated gene-1 (AEG-1) is elevated in multiple human cancers including brain tumors, neuroblastomas, melanomas, breast cancers, non-small cell lung cancers, liver cancers, prostate cancers, and esophageal cancers. This gene plays crucial roles in tumor cell growth, invasion, angiogenesis and progression to metastasis. In addition, over-expression of AEG-1 protects primary and transformed cells from apoptosis-inducing signals by activating PI3K-Akt signaling pathways. These results suggest that AEG-1 is intimately involved in tumorigenesis and may serve as a potential therapeutic target for various human cancers. However, the normal physiological functions of AEG-1 require clarification. We presently analyzed the expression pattern of AEG-1 during mouse development. AEG-1 was expressed in mid-to-hindbrain, fronto-nasal processes, limbs, and pharyngeal arches in the early developmental period from E8.5 to E9.5. In addition, at stages of E12.5-E18.5 AEG-1 was localized in the brain, and olfactory and skeletal systems suggesting a role in neurogenesis, as well as in skin, including hair follicles, and in the liver, which are organ sites in which AEG-1 has been implicated in tumor development and progression. AEG-1 co-localized with Ki-67, indicating a role in cell proliferation, as previously revealed in tumorigenesis. Taken together, these results suggest that AEG-1 may play a prominent role during normal mouse development in the context of cell proliferation as well as differentiation, and that temporal regulation of AEG-1 expression may be required during specific stages and in specific tissues during development.
星形胶质细胞上调基因1(AEG-1)在多种人类癌症中表达升高,包括脑肿瘤、神经母细胞瘤、黑色素瘤、乳腺癌、非小细胞肺癌、肝癌、前列腺癌和食管癌。该基因在肿瘤细胞生长、侵袭、血管生成以及向转移进展过程中发挥关键作用。此外,AEG-1的过表达通过激活PI3K-Akt信号通路保护原代细胞和转化细胞免受凋亡诱导信号的影响。这些结果表明,AEG-1与肿瘤发生密切相关,可能是各种人类癌症的潜在治疗靶点。然而,AEG-1的正常生理功能尚需阐明。我们目前分析了AEG-1在小鼠发育过程中的表达模式。在胚胎发育早期从E8.5到E9.5,AEG-1在中脑至后脑、额鼻突、四肢和咽弓中表达。此外,在E12.5-E18.5阶段,AEG-1定位于脑、嗅觉和骨骼系统,提示其在神经发生中发挥作用,同时也定位于皮肤(包括毛囊)和肝脏,而这些器官部位已证实AEG-1与肿瘤发生和进展有关。AEG-1与Ki-67共定位,表明其在细胞增殖中发挥作用,正如先前在肿瘤发生中所揭示的那样。综上所述,这些结果表明,AEG-1在正常小鼠发育过程中,在细胞增殖以及分化方面可能发挥重要作用,并且在发育过程中的特定阶段和特定组织中可能需要对AEG-1的表达进行时间调控。