The role of amphiregulin in breast cancer.
Amphiregulin (AR) is an epidermal growth factor (EGF)-related peptide that operates exclusively through the EGF receptor and that can bind to heparin. AR also possesses nuclear localization sequences in the extended NH2-terminal region suggesting an additional intracellular site of action. AR mRNA and protein expression have been detected in primary human mammary epithelial cell strains, nontransformed human mammary epithelial cell lines, several human breast cancer cell lines, and primary human breast carcinomas. The frequency and levels of AR protein expression are generally higher in invasive breast carcinomas than in ductal carcinomas in situ or in normal, noninvolved mammary epithelium. In addition, AR can function as an autocrine and/or juxtacrine growth factor in human mammary epithelial cells that have been transformed by an activated c-Ha-ras proto-oncogene or by overexpression of c-erb B-2. AR expression is also enhanced by mammotrophic hormones such as estrogens and other growth factors such as EGF.
Salomon
D S
DS
Tumor Growth Factor Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Normanno
N
N
Ciardiello
F
F
Brandt
R
R
Shoyab
M
M
Todaro
G J
GJ
D000595:Amino Acid Sequence; D066258:Amphiregulin; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D066255:EGF Family of Proteins; D066246:ErbB Receptors / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics* / Q000502:physiology; D006133:Growth Substances / Q000235:genetics* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas
C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D066246:ErbB Receptors