Proepiregulin
positive regulation of DNA replication
Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family.
We have recently identified epiregulin as a new growth regulator and a member of the epidermal growth factor (EGF) family. Epiregulin has certain characteristics that are different from those of the classical members of the EGF family, EGF and transforming growth factor alpha, including mitogenic responses on several normal cells and binding to EGF receptors on epidermoid carcinoma A431 cells. In the present study we cloned and identified the expression of human epiregulin transcript. The human epiregulin gene encoded a 163-residue putative transmembrane precursor containing an EGF-like domain in the internal segment, and the structural organization was similar to that of other members of the EGF family that bind to EGF receptors. Northern blot analysis showed the expression of human epiregulin to be mainly on peripheral blood macrophages and the placenta in normal tissues, and was highest on epithelial tumour cell lines in various types of tumour cell lines. The expression profile was quite different from that of other members of the EGF family in normal and tumour cells. Recombinant expression in mammalian cells also showed that human epiregulin was secreted as a soluble form of approx. 5 kDa that is biologically active on the basis of the stimulation of DNA synthesis. Our findings suggest that epiregulin is involved in certain physiological processes such as maintenance or development of normal cell growth, and the progression of carcinomas.