Epidermal growth factor-related peptides in the pathogenesis of human breast cancer.
A number of different epidermal growth factor (EGF)-related peptides such as EGF, transforming growth factor alpha (TGF alpha), amphiregulin (AR), heregulin (HRG), and cripto-1 (CR-1), are coexpressed to varying degrees in both normal and malignant mammary epithelial cells. However, in general the frequency and level of expression of TGF alpha, AR, and CR-1 are higher in malignant breast epithelial cells than in normal mammary epithelium. In addition, several of these peptides such as TGF alpha and AR can function as autocrine and/or juxtacrine growth factors in mammary epithelial cells, and their expression is stringently regulated by mammotrophic hormones such as estrogens, activated proto-oncogenes that have been implicated in the pathogenesis of breast cancer, and other growth factors. The redundancy of expression that is observed for a number of these structurally related peptides in both normal and malignant mammary epithelial cells suggests that some of these peptides may be involved in regulating other aspects of cellular behavior such as differentiation in addition to proliferation.
Normanno
N
N
Tumor Growth Factor Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Ciardiello
F
F
Brandt
R
R
Salomon
D S
DS
D000595:Amino Acid Sequence; D066258:Amphiregulin; D014408:Biomarkers, Tumor; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000737:chemistry; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000096:biosynthesis / Q000737:chemistry; D006133:Growth Substances / Q000096:biosynthesis / Q000737:chemistry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000737:chemistry; D020880:Neuregulins; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000737:chemistry
D066258:Amphiregulin; D014408:Biomarkers, Tumor; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D020880:Neuregulins; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; C587848:AREG protein, human; C070636:TDGF1 protein, human