Tuberc Respir Dis.  1999 Sep;47(3):347-355.

Increased Expression of Phospholipase C-gamma1 Activator Protein, AHNAK in Human Lung Cancer Tissues

• Oh YJ
• Park CS
• Choi SY
• Cheong SC
• Lee SM
• Hwang SC
• Lee YH
• Hahn MH
• Lee KB
• Ryu HY
• Bae YS
• Rhee SG

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.

Keyword

PLC; PLC-gamma1; AHNAK protein; tau protein; lung cancer; oncogenesis

MeSH Terms

Arachidonic Acid
Blotting, Western
Brain
Carcinogenesis
Humans*
Hydrolysis
Immunohistochemistry
Inositol
Isoenzymes
Lung Neoplasms*
Lung*
Molecular Weight
Phosphatidic Acids
Phosphatidylinositols
Phospholipases*
Protein-Tyrosine Kinases
Proteolysis
Second Messenger Systems
Signal Transduction
tau Proteins
Arachidonic Acid
Inositol
Isoenzymes
Phosphatidic Acids
Phosphatidylinositols
Phospholipases
Protein-Tyrosine Kinases
tau Proteins