Hijazi M M, Young P E, Dougherty M K, Bressette D S, Cao T T, Pierce J H, Wong L M, Alimandi M, King C R
Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Int J Oncol. 1998 Nov;13(5):1061-7. doi: 10.3892/ijo.13.5.1061.
Ligands of the EGF/Heregulin family control the growth of epithelial cells by binding to receptors of the erbB family. By searching a large database of cDNA sequences at Human Genome Sciences Inc. we have identified a new encoded protein sequence containing all the conserved elements of the EGF/Heregulin family. The same sequence has recently been independently identified as NRG-3. The EGF-like domain of NRG-3 was generated as a recombinant protein in E. coli and used to test the specificity of receptor binding. In human breast cancer cells and in 32D cells transfected by erbB family members, NRG-3 activated multiple erbB family members. These include EGF receptor (erbB1) and erbB4 when expressed individually and erbB2 and erbB3 when expressed together. Recombinant 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 and malignant breast epithelial cells in vivo.
表皮生长因子/神经调节蛋白（EGF/Heregulin）家族的配体通过与erbB家族的受体结合来控制上皮细胞的生长。通过搜索人类基因组科学公司的一个大型cDNA序列数据库，我们鉴定出了一种新的编码蛋白序列，它包含EGF/Heregulin家族所有的保守元件。同一序列最近被独立鉴定为NRG-3。NRG-3的表皮生长因子样结构域在大肠杆菌中作为重组蛋白产生，并用于测试受体结合的特异性。在人乳腺癌细胞和由erbB家族成员转染的32D细胞中，NRG-3激活了多个erbB家族成员。当单独表达时，这些成员包括表皮生长因子受体（erbB1）和erbB4；当共同表达时，包括erbB2和erbB3。重组NRG-3改变了体外培养的人乳腺癌细胞的生长。NRG-3在源自乳腺癌的细胞系中表达。这些结果表明，NRG-3在体内是正常和恶性乳腺上皮细胞的潜在调节因子。
