NRG-3 IN HUMAN BREAST CANCERS - ACTIVATION OF MULTIPLE ERBB FAMILY PROTEINS

Ligands of the EGF/Heregulin family control the growth of epithelial c ells by binding to receptors of the erbB family. By searching a large database of cDNA sequences at Human Genome Sciences Inc. we have ident ified a new encoded protein sequence containing all the conserved elem ents of the EGF/Heregulin family. The same sequence has recently been independently identified as NRG-3. The EGF-like domain of NRG-3 was ge nerated as a recombinant protein in E. coli and used to test the speci ficity of receptor binding. In human breast cancer cells and in 32D ce lls transfected by erbB family members, NRG-3 activated multiple erbB family members. These include EGF receptor (erbB1) and erbB4 when expr essed individually and erbB2 and erbB3 when expressed together. Recomb inant NRG-3 altered the growth of human breast cancer cells growing in vitro. NRG-3 was expressed in cell lines derived from breast cancer. These results indicate that NRG-3 is a potential regulator of normal a nd malignant breast epithelial cells in vivo.