Tuberc Respir Dis > Volume 47(3); 1999 > Article
Tuberculosis and Respiratory Diseases 1999;47(3):347-355.
DOI: https://doi.org/10.4046/trd.1999.47.3.347    Published online September 1, 1999.
Increased Expression of Phospholipase C-gamma1 Activator Protein, AHNAK in Human Lung Cancer Tissues.
Yoon Jung Oh, Chun Seong Park, So Yeon Choi, Seong Cheoll Cheong, Sun Min Lee, Sung Chul Hwang, Yi Hyeong Lee, Myung Ho Hahn, Kyi Beom Lee, Han Young Ryu, Yoon Su Bae, Seo Goo Rhee
1Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Korea.
2Department of Anatomic Pathology, Ajou University School of Medicine, Suwon, Korea. schwang@madang.ajou.ac.kr
3Department of Thoracic Surgery, Ajou University School of Medicine, Suwon, Korea.
4Department of Laboratory of Medical Genetics, Ajou University School of Medicine, Suwon, Korea.
5Department of Biological Sciences, Ewha Womans University, Korea.
6Laboratory of Cell Signaling, National Institutes of Health, Bethesda, M.D., U.S.A.
Abstract
BACKGROUND
Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate(PIP2) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate(IP3) and diacylglycerol. PLC-gamma1, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-gamma1 have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by IP3, phosphatidic acid, etc. Very recently, another PLC-gamma1 activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-gamma1 activator, AHNAK, in lung cancer specimens and their paired normal. METHODS: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract. Immunohistochemical stain was performed with primary antibody against AHNAK protein. RESULTS: Twenty-two among twenty-eight lung cancer tissues showed over expression of AHNAK protein(eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomal). the resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot. CONCLUSION: The overexpression of PLC-gamma1 activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-gamma1 act in concerted manner in carcinogenesis.
Key Words: PLC, PLC-gamma1, AHNAK protein, tau protein, lung cancer, oncogenesis


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