Identification of Cripto-1 in human milk.
Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related peptide that plays an important role in normal mammary gland development. CR-1 is expressed in the growing terminal end buds in the virgin mouse mammary gland and its expression increases during pregnancy and lactation. Furthermore, CR-I is involved in the early stages of mouse mammary tumorigenesis and in the pathogenesis of human breast cancer. Since CR-1 is expressed in the mouse mammary gland at high levels during pregnancy and lactation, we have evaluated whether this protein is present in human milk. In the present study we demonstrate that a 28 kDa immunoreactive CR-1 protein is present in 24 human milk samples as assessed by western blot analysis and that by enzyme-linked immunosorbent assay the concentration of CR-1 ranges between 62 and 118 ng/ml. In addition, CR-1 that had been purified from human milk is able to stimulate the phosphorylation of mitogen activated protein kinase in nontransformed NMuMG mouse mammary epithelial cells. These results suggest that CR-1 in human milk may be important in regulating mammary gland development during pregnancy and lactation.
Bianco
C
C
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA.
Wechselberger
C
C
Ebert
A
A
Khan
N I
NI
Sun
Y
Y
Salomon
D S
DS
D000818:Animals; D014408:Biomarkers, Tumor / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D058851:GPI-Linked Proteins; D006133:Growth Substances / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D051379:Mice; D008895:Milk, Human / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human; C489450:Tdgf1 protein, mouse; D004815:Epidermal Growth Factor; D020929:Mitogen-Activated Protein Kinase Kinases