Role of tyrosine specific phosphorylation of cellular proteins, especially EGF receptor and p125FAK in human lung cancer cells.
To clarify the role of tyrosine phosphorylation of cellular proteins in human lung cancer cells, phosphotyrosine (PTYR)-containing proteins in lung cancer cell lines and in paired tissues resected from cancerous and normal lungs were studied by immunoblotting with an anti-PTYR antibody. We found that the profiles of protein phosphorylation were very similar among those cell lines which had different histological features. The major PTYR-containing proteins (180-190 KDa, 120-130 KD, and 95-100 KDa) were detected in lung cancer cell lines. The expression of EGF receptor (EGF-r) (p185) and o-erb B2 protein, and tyrosine phosphorylation of p125FAK were examined in cancerous lung tissues and normal lung tissues. In surgical specimens, approximately half of the samples of lung cancer tissues showed clear elevation of tyrosine phosphorylation. In these cancerous tissues, no clear amplification of EGF-r and c-erb B2 protein expression was observed. However, elevation of tyrosine phosphorylation of p125FAK was observed in cancerous lung tissues but not in normal lung tissues, and its phosphorylation was closely correlated with the nodal involvement of cancer and disease-free survival time. These results suggested that the intracellular signaling pathway via tyrosine phosphorylation plays a role in the generation and immortalization of lung cancer, and assessment of tyrosine phosphorylation of cellular proteins. especially p125FAK, may be available clinically as a prognostic factor.
Imaizumi
M
M
Department of Thoracic Surgery, Nagoya University School of Medicine, Japan.
Nishimura
M
M
Takeuchi
S
S
Murase
M
M
Hamaguchi
M
M
D000328:Adult; D000368:Aged; D015815:Cell Adhesion Molecules / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000502:physiology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008175:Lung Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000032:analysis; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C496050:PTK2 protein, human