Alterations in the level of phosphotyrosine signal transduction constituents in human parotid tumors.
Human parotid tumors were evaluated for the activation of the phosphotyrosine signaling pathway by Western blot, enzyme activity assay, and reverse transcriptase-polymerase chain reaction. Warthin's tumor and mucoepidermoid carcinomas had the greatest level of tyrosine phosphorylated proteins identified in plasma membrane fractions. These tumors, along with pleomorphic adenocarcinoma, showed high levels of membrane expression of the tyrosine kinase receptor, c-erbB-2, and phosphatidylinositol-3-kinase. Expression of the epidermal growth factor receptor was confined to normal tissue. The level of mRNA for c-erb was elevated only in mucoepidermoid carcinomas. Messenger RNA levels for ras were unchanged from control levels in all tumors, while the level of src mRNA was higher in the tumor samples than the normal parotid tissue. The activities of several signal transduction kinases, including protein kinase A and C were elevated in tumor tissue (7.7- to 18.9- and 0.4- to 3.7-fold higher, respectively), relative to surrounding normal tissue. While the level of glandular amylase was reduced (22%-0% of normal levels) in the tumor tissue, epidermal growth factor (EGF) and transforming growth factor-alpha (TGFalpha) content was dramatically higher in the neoplastic tissue (10- to 170-fold and 4.6- to 6.0-fold, respectively). These results suggest that with the presence of elevated levels of EGF, TGFalpha, and the oncoprotein receptor c-erbB-2 in the membrane of parotid tumors, cell proliferation and activation of the phosphotyrosine signal transduction pathway may involve autocrine stimulation through the expression of high levels of growth factor and receptor in the same tissue.
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Department of Oral Biology, University of Florida, Gainesville, 32610 USA.
Purushotham
K R
KR
Kerr
M
M
Tao
Z
Z
Jonsson
R
R
Olofsson
J
J
Humphreys-Beher
M G
MG
D001483:Base Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004815:Epidermal Growth Factor / Q000032:analysis; D006801:Humans; D008969:Molecular Sequence Data; D010307:Parotid Neoplasms / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha / Q000032:analysis
D017868:Cyclic AMP-Dependent Protein Kinases; D004815:Epidermal Growth Factor; D019000:Phosphotyrosine; D011493:Protein Kinase C; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha