Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas.
Phospholipase C-gamma 1 (PLC-gamma 1) is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. However, the biological significance of this molecule in normal or malignant human epithelial cell proliferation is unknown. We determined the relative content of PLC-gamma 1 in primary human mammary carcinomas and in nonmalignant mammary tissues. By Western blot and immunohistochemistry, considerably higher levels of PLC-gamma 1 protein were detectable in the majority of carcinomas and in one of two benign fibroadenomas compared to normal breast tissues. In 18 of 21 carcinomas that contained high levels of PLC-gamma 1, the presence of phosphotyrosine on PLC-gamma 1 could also be detected. All carcinomas in which tyrosine phosphorylated PLC-gamma 1 was present also expressed detectable levels of the epidermal growth factor receptor or erbB-2, two tyrosine kinases known to phosphorylate this enzyme. Thus, a high percentage of mammary carcinomas concomitantly display increased levels of receptor tyrosine kinases and a direct tyrosine phosphorylation substrate, thereby potentially amplifying two successive steps in a signal transduction pathway.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
C L
CL
Arteaga
M D
MD
Johnson
G
G
Todderud
R J
RJ
Coffey
G
G
Carpenter
D L
DL
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D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D001940:Breast / Q000201:enzymology / Q000473:pathology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005348:Fibrocystic Breast Disease / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007106:Immune Sera; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases; D012016:Reference Values; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000032:analysis / Q000378:metabolism*
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D007106:Immune Sera; D007527:Isoenzymes; D010455:Peptides; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D010738:Type C Phospholipases