A NOVEL EPITHELIAL-EXPRESSED ETS GENE, ELF3 - HUMAN AND MURINE CDNA SEQUENCES, MURINE GENOMIC ORGANIZATION, HUMAN MAPPING TO 1Q32.2 AND EXPRESSION IN TISSUES AND CANCER

The ETS family of genes are implicated in cancers such as Ewings sarco ma, acute myeloid leukemia and chronic myelomoncytic leukemia. Further , they have important functions in embryonic development. Hence, ident ification and characterization of members of this family are important . We identify a novel ETS family member, ELF3, and report its human an d murine cDNA sequences. The mouse cDNA has an alternatively spliced t ranscript with an extra 60 bp inserted. Hence we present the organizat ion of the murine Elf3 gene together with its exon/intron structure. T his gene consists of 9 exons and 8 introns spanning 4.8 kb. ELF3 binds and transactivates ETS sequences and interestingly also shows the abi lity to bind a GGAT-Iike purine core, a preferential ETS1/ETS2 type bi nding site. The expression of ELF3, unlike most other ETS family membe rs, is absent in hematopoietic cells and hematopoietic organs in human s and mice. Intriguingly, the gene is specifically expressed in cell l ines of epithelial origin and in organs such as lung, stomach, intesti ne, kidney that have specialized epithelial cells. We localize the hum an gene to 1q32.2, a region that is amplified in epithelial tumors of the breast, lung and prostate. Finally, we show that ELF3 expression i s increased in a lung carcinoma and adenocarcinoma, as compared to nor mal tissue. ELF3 is also expressed in cell lines derived from lung can cers. These results suggest that this novel ETS gene may be involved i n lung tumorigenesis.