A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines

Abstract

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 di erent 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-likefactor) 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-speci®c 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 ®nd 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 speci®c 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.

Microarray Analysis Reveals Distinct Gene Expression Profiles Among Different Tumor Histology, Stage and Disease Outcomes in Endometrial Adenocarcinoma

“…Trefoil factor 3 (TFF3) , located at 21q22.3, belongs to a family of small mucin-associated polypeptides that can regulate cancer progression by increasing tumor metastasis [16], [17], [21], [22]. E74-like factor 5 (ELF5) or epithelium –specific ETS factor 2 (ESE2) , located at 11p15-p13, is a member of the ETS family of transcription factors and has been implicated to play a key role in cell proliferation, differentiation, apoptosis and tumorigenesis [17], [23].…”

Epithelium-specific ets transcription factor 2 upregulates cytokeratin 18 expression in pulmonary epithelial cells through an interaction with cytokeratin 18 intron 1

“…Ese-2-ets was able to bind 11 of the possible 18 K18 intron 1 EBSs that were identified by their 5'-GGAA-3' core (Fig. 4), a core region which has been shown to be preferable for Ese-2 binding [6,11]. Ese-2-ets bound with the highest strength to oligonucleotides A, F, Q, and E74, intermediate strength to oligonucleotides E, G, K, and N, and bound weakly to oligonucleotides D, H, I, and J (Fig.…”

“…Identifying a consensus recognition sequence of Ese-2 using DNA oligonucleotides containing the EBSs of K18 intron 1 Ese-2 has been described to bind to an EBS with a core of 5'-GGAA-3' [6,11]. This implies that, for Ese-2, there are 18 possible EBSs within the first intron of K18 (Fig.…”

“…Since then, more than 30 Ets family members have been identified [2,3]. These proteins are expressed mainly in hematopoietic cells [4,5], however some are also expressed in epithelial cells [6][7][8][9][10][11]. Ets factors are known to play roles in skeletal development, haematopoiesis, neural synapse formation, immunomodulation, metastasis, cellular proliferation and differentiation, and apoptosis [12][13][14].…”

“…Under normal physiological conditions, Ese-2 and other members of the ESE subfamily are expressed solely in epithelial cells. Human Ese-2 and its mouse homolog, Elf5, have an amino acid identity of 95% [11], and both have an expression pattern that is restricted to differentiated keratinocytes and glandular epithelium [6]. The ETS domain of Ese-2, which recognizes a 5'-GGAA-3' core EBS, is located at the C-terminus of the protein [6,11].…”