Zhou J, Ng A Y, Tymms M J, Jermiin L S, Seth A K, Thomas R S, Kola I
Molecular Genetics and Development Group, Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia.
Oncogene. 1998 Nov 26;17(21):2719-32. doi: 10.1038/sj.onc.1202198.
The ETS transcription factors are a large family implicated in the control of cellular proliferation and tumorigenesis. In addition, chromosomal translocations involving ETS family members are associated with a range of different human cancers. Given the extensive involvement of ETS factors in tumorigenesis, it becomes important to identify any additional ETS genes that may also play oncogenic roles. We identify a novel gene, ELF5, that appears to belong to the ELF (E74-like-factor) subfamily of the ETS transcription factor family, based upon similarity within the 'ETS domain'. ELF5 displays a similar, but more restricted, expression pattern to that of the newly isolated epithelium-specific ETS gene, ELF3. Unlike most other ETS family members, ELF5 is not expressed in hematopoietic compartments, but is restricted to organs such as lung, stomach, kidney, prostate, bladder and mammary gland. ELF5 is localized to human chromosome 11p13-15, a region that frequently undergoes loss of heterozygosity (LOH) in several types of carcinoma, including those of breast, kidney and prostate. We find that ELF5 expression is not detectable in a number of carcinoma cell lines, some of which display loss or rearrangement of an ELF5 allele. Similar to other ETS family members, ELF5 displays specific binding to DNA sequences containing a GGAA-core. In addition, ELF5 is able to transactivate through these ETS sequences, present upstream from a minimal promoter. Our data suggest that ELF5 may play roles in mammary, lung, prostate and/or kidney function, and possibly also in tumorigenesis.
ETS转录因子是一个大家族,与细胞增殖和肿瘤发生的调控有关。此外,涉及ETS家族成员的染色体易位与一系列不同的人类癌症相关。鉴于ETS因子广泛参与肿瘤发生,识别任何可能也发挥致癌作用的其他ETS基因变得很重要。我们鉴定出一个新基因ELF5,基于“ETS结构域”内的相似性,它似乎属于ETS转录因子家族的ELF(E74样因子)亚家族。ELF5显示出与新分离的上皮特异性ETS基因ELF3相似但更局限的表达模式。与大多数其他ETS家族成员不同,ELF5不在造血区室中表达,而是局限于肺、胃、肾、前列腺、膀胱和乳腺等器官。ELF5定位于人类染色体11p13 - 15,该区域在包括乳腺癌、肾癌和前列腺癌在内的几种类型的癌症中经常发生杂合性缺失(LOH)。我们发现在一些癌细胞系中检测不到ELF5的表达,其中一些显示出ELF5等位基因的缺失或重排。与其他ETS家族成员类似,ELF5显示出与含有GGAA核心的DNA序列特异性结合。此外,ELF5能够通过这些位于最小启动子上游的ETS序列进行反式激活。我们的数据表明ELF5可能在乳腺、肺、前列腺和/或肾功能中发挥作用,也可能在肿瘤发生中发挥作用。