Expression of Phospholipase C-gamma1 and gamma2 in Non-Hodgkin's and Hodgkin's Lymphoma

Phospholipase C (PLC) plays a role in ligand-mediated signal transduction for cellular activity such as proliferation and differentiation. A recent observation that PLC- gamma1 is highly expressed in some kinds of human cancer tissue supports the view that PLC-gamma1 may be involved in proliferation and carcinogenesis. PLC-gamma2 is known to be involved in B cell differentiation and maturation. However, there have been few studies about the expressions of PLC-gamma1 and gamma2 in human lymphoid malignancy. In the present study, we examined the contents of PLC-gamma1 and gamma2 in 10 cases of B cell, 10 cases of T cell non-Hodgkin's lymphoma and 5 cases of Hodgkin's lymphoma to find out whether these enzymes play any role in the carcinogenesis by immunohistochemistry and immunoprecipitation. Immunoprecipitation analysis revealed that in contrast to increased expression of PLC-gamma2 only in B cell lymphoma, a considerably higher level of PLC-gamma1 was detected in both B and T cell lymphoma. Immunohistochemical finding confirmed this observation. PLC-gamma1 and PLC-gamma2 were expressed in the cytoplasm of most tumor cells. PLC-gamma2 was also expressed in mature B cells, while PLC-gamma1 was not expressed in reactive non-tumor cells. These results suggest that PLC-gamma1 mediated signal transduction implicates a significant role in the carcinogenesis of all types of lymphoid tissue, and PLC-gamma2 may play a role in the carcinogenesis of B cell lymphoma as well as B cell differentiation.

Signal Transduction System of Experimentally Induced Cholesteatoma in the Mongolian Gerbil / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Hyperproliferative character of the cholesteatoma in the middle ear seems to be related to epithelial cell proliferation and differentiation. The proliferation of cells, their differentiation and organization in specialized tissues and the expression of their differentiated properties are under control of a large number of regulatory processes and complex interactions called signal transduction. PLC-gamma1 is a substrate of protein kinase located in EGFR, PDGFR-alpha and -beta and signal transduction through PLC-gamma1 participates in the regulation of cell growth and differentiation. This study was undertaken to investigate the distribution of PLC-gamma1, EGFR and PDGFR in experimentally induced cholesteatoma, deep meatal skin and retroauricular skin of Mongolian gerbil. MATERIALS AND METHODS: Using Western blotting and immunohistochemical techniques, we investigated the reaction patterns of antibody to PLC-gamma1, EGFR, PDGFR-alpha and PDGFR-beta as a proliferation and differentiation marker in the experimentally induced cholesteatoma matrices of Mongolian gerbil. For the control, same study was performed with deep meatal skin and retrosuricular skin. RESULTS: By Western blotting, considerably higher levels of PLC-gamma1, EGFR protein were detectable in cholesteatoma compared with control, however, PDGFR-alpha and -beta were not detected in cholesteatoma The immunostaining intensity of PLC-gamma1 and EGFR at suprabasal cell layer and basal cell layer were intense in cholesteatoma than in control. PDGFR-alpha and -beta were not detected in both cholestatoma and control. CONCLUSION: Over-expression of PLC-gamma1 and EGFR in induced cholesteatomas may contribute abnormal proliferation and differentiation of their epithelial cell. Authors suggest that induced cholesteatoma in Mongolian gerbils can be a good model of signal transduction study for cholesteatoma.

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

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.

Expression of Phospholipase C-beta1 and Phospholipase C-gamma1 on Cholesteatoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: A histological finding that is the most characteristic of cholesteatoma is the proliferation of the squamous cell. Signal transduction through phospholipase C(PLC) participates in the regulation of epidermal cell growth and differentiation. EGF, PDGF, and TGF-alpha bind to their receptors and thereby induce tyrosine phosphorylation of the phospholipase C-gamma1 (PLC-gamma1). PLC-gamma1 is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. Tyrosine kinase phosphorylation of PLC-gamma1 stimulates PLC activation and cell proliferation. The G-protein has been shown to specifically activate PLC-beta1. However, the signal transduction pathway and the significance of PLC in cholesteatoma is unknown. This study attempted to provide some evidence that PLC plays a role in cholesteatoma by investigating the distribution and quantity of PLC-beta1 and PLC-gamma1 in the posterior auricular skin and cholestsatoma. MATERIALS AND METHODS: Western blotting and immunohistochemical study were performed for 20 cholesteatoma specimens obtained from patients who underwent operation. RESULTS: Western blot analyses revealed that PLC-beta1 protein and PLC-gamma1 protein were detectable in cholesteatoma and that these proteins were in higher levels compared with the control. In the imm-unohistochemical study, PLC-gamma1 was detected in the horny cell layer of posterior auricular skin but not in the suprabasal layer and the horny cell layer of cholesteatoma. PLC-beta1 was detected in the primary basal layer and a minor reaction was also noted in the spinous layer of posterior auricular skin. However, there were detactable reactions in both the basal and the suprabasal layers of cholesteatoma. CONCLUSION: The results of this study suggest that there are signal transduction pathways through PLC, over-expression of PLC, the different signaling mechanism by PLC in the basal and the suprabasal layer of cholesteatoma.

Expressions of Vascular Endothelial Growth Factor (VEGF), Phospholipase C-gammal and Ki-67 in Squamous Cell Carcinoma and High Grade Squamous Intraepithelial Lesion of Uterine Cervix

Angiogenesis is an early event in tumorigenesis and facilitates tumor progression and metastasis. This study was performed to evaluate the expression of vascular endothelial growth factor (VEGF), phospholipase C-gamma1 (PLC-gamma1) and Ki-67, and to assess the relationship between them in cervical squamous cell neoplasia. The materials were fifty cervical squamous cell lesions, consisted of thirty HSIL (6 moderate dysplasia, 11 severe dysplasia, 13 carcinoma in situ), and twenty invasive squamous cell carcinoma (ISCC) cases. Immunohistochemical stain for VEGF, PLC-gamma1 and Ki-67 were done. Expression rate of VEGF was significantly higher in ISCC than in HSIL (p=0.012). PLC-gamma1 expression was significantly higher in ISCC than in HSIL (p=0.004). Ki-67 labelling index was significantly higher in ISCC than in HSIL (p=0.001) and higher in VEGF-positive tumors than in VEGF-negative tumors (p=0.018), but there were no significant differences between PLC-gamma1 expression and Ki-67 labelling index (p>0.05), and between PLC-gamma1 and VEGF (p>0.05). This study suggests that PLC-gamma1 and VEGF may play an important role in tumor cell proliferation and invasion, and these may be a useful marker to predict the possibility of invasion in cervical cancer.

The Expression of Phospholipase C-gamma1 and Its Cellular Characteristics / 대한암학회지

BACKGROUND: The activation of phospholipase C(PLC) is one of the early cellular events in various growth process, including malignant transformation. PLC-gamma1 is activated through direct interaction with growth factor receptor tyrosine kinase. MATERIAL AND METHODS: Using immunoblot assay, we evaluated overexpression of PLC-gamma1 expression in twenty human breast cancer tissues. It was also determined whether there was any connection between other prognostic factors(numbers of metastatic axillary nodes, nuclear and histological grade, c-erbB2, p53 and E-cadherin) and the overexpression of PLC-gamma1 protein. RESULTS: Seventeen of 20 breast cancer tissues showed overexpression of PLC-gamma1, which was corresponded to that seen on the immunohistochemistry( kappa= 0.8275, p = 0.003). Of 3 tumor markers, immunohistochemically determined, positive expression of E-cadherin only was associated with PLC-gamma1 protein overexpression in a range of statistical significance (p=0.045, kappa=0.607). CONCLUSION: PLC-gamma1 overexpression might be pathogenic trigger involved in breast cancer and the relationship between expression of E-cadherin and PLC-gamma1 would require further elucidation.

Value of Phospholipase C gamma-1, Epidermal Growth Factor Receptor, and Her-2/neu in Human Breast Cancer / 대한암학회지

PURPOSE: Oncogen or growth factor receptor such as phospholipase C isoenzyme gamma-1 (PLC gamma-1), epidermal growth factor receptor (EGFR), and Her-2/neu which related with tyrosin kinasemay and then regulating vell proliferation may have a role as prognostic factors for breast cancer. MATERIAL AND METHODS: With assumption that expression of PLC gamma-1, EGFR and Her-2/neu oncogene has close relationship with prognosis of breast cancer, 59 breast cancer patients who were operated upon at Korea University Hospital during a period of 6 years starting June 1988 to May 1994 were selected for this study. This study was carried out by comparing between expression of PLC gamma-1, EGFR and Her-2/neu oncogene and patient's survival rate. These expression were also compared with TNM system, estrogen and progesterone receptor and at same time these expressions were compared with each other to see whether there are any relationship among these expression. RESULTS: Expression of PLC gamma-1, EGFR and Her-2/neu were present in 42% (25/59), 46% (27/59) and 20% (12/59). The expression of PLC gamma-1 was closely related with the expression of EGFR (p0.05). The expression of EGFR was closely related with the expression of Her-2/neu (p0.05). The expression of Her-2/neu was not closely related with hormone receptors and TNM stage except axillary lymph node metastasis. There were close relationship between overall and disease free survival and PLC gamma-1 and Her-2/neu. But EGFR had only related with disease free survival rate. CONCLUSION: In conclusion, the expression of PLC gamma-1, EGFR and Her-2/neu oncogene in human breast cancer may be useful prognostic factors independently and it may potentiated its individual value as a prognostic factors if use them together.

The Expression of phospholipase C-lambda1 and p53 in Endometrial Carcinoma / 대한부인종양콜포스코피학회잡지

PLC-gamma1 plays a central role in the signal transduction for cellular activity, such as proliferation and differentiation. However, the significance of their expressions in endometrial cancer is yet to be determined. The current study examined the expression prevalence of phospholipase C-gamma1(PLC-gamma1) , and studied its relationship with p53 expression in endometrial carcinomas of varying stages and grades. Expressions of PLC-gamma1 and p53 were determined using immunohistochemical taining of paraffin embedded tissues from 21 endometrial specimens; Specimens included 10 cases of grade I, 8 cases of grade II, and 3 cases of grade III lesions. While there were few PLC-gamma1 expressions in the control group, 60% (6/10) of grade I carcinomas showed obvious PLC-gamma1 expression, 50%, and 30% of Grade II and III cases did respectively. In addition, PLC-gamma1 expression was restricted to the tumor lesions and the intensity of the PLC-lambda1 was the strongest in well differentiated cancers. P53 expression was identified in 7 of 21 (33%) cases, and there was no relationship between PLC-gamma1 expression and p53 overexpression. Our studies revealed that levels of PLC-gamma1 play important roles in the occurrence of ndometrial carcinomas, though factors that might influence them still remain obscure. And also further studies about correlation between PLC-gamma1 and p53 are needed to elucidate that in tumorigenesis.