The identification of novel endothelial-derived genes is important in the study of angiogenesis, and may have potential uses in cancer diagnosis and treatment. We performed SSH (suppression subtractive hybridization) on control HUVECs (human umbilical vein endothelial cells) versus HUVECs exposed to tumor-conditioned media. We found that a novel cDNA (GenBank Accession No. AF358829) is differentially expressed in endothelial cells on Northern analysis, and named it endothelial-derived gene-l (EG-1). This gene product is predicted to encode a 178-aa, 19.5-kDa protein, and is localized to chromosome 4. It has some homology to a mouse cDNA (94%) and a Drosophila cDNA (31%). On Northern analysis, endothelial cells express two EG-1 RNA species (1.2 and 2.4 kb). The expression of either transcripts is upregulated by endothelial cells when exposed to tumor conditioned media. This phenomenon is observed only under sparse conditions (50% confluency). Transcripts are present abundantly in highly vascular tissues such as placenta, testis, and liver. Interestingly, both Northern analysis and in situ hybridization studies show that this gene is expressed in other cell types as well, predominantly the epithelial type. Breast cancer, prostate cancer, and colon cancer cells show elevated expression of the higher 2.4-kb RNA form. Our data suggest that EG-1 is associated with a stimulated state in endothelial and epithelial cells, and may have a role in tumor angiogenesis. (C) 2002 Elsevier Science.