NRG-3 in human breast cancers: activation of multiple erbB family proteins.
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.
Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
M M
MM
Hijazi
P E
PE
Young
M K
MK
Dougherty
D S
DS
Bressette
T T
TT
Cao
J H
JH
Pierce
L M
LM
Wong
M
M
Alimandi
C R
CR
King
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D016208:Databases, Factual; D004815:Epidermal Growth Factor / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D020880:Neuregulins; D018739:Oncogene Proteins v-erbB / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C486357:NRG3 protein, human; D020880:Neuregulins; D018739:Oncogene Proteins v-erbB; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor