FGF-2, TGFâ-1, PDGF-A and respective receptors expression in pleomorphic adenoma myoepithelial cells: an in vivo and in vitro study

Myoepithelial cells have an important role in salivary gland tumor development, contributing to a low grade of aggressiveness of these tumors. Normal myoepithelial cells are known by their suppressor function presenting increased expression of extracellular matrix genes and protease inhibitors. The importance of stromal cells and growth factors during tumor initiation and progression has been highlighted by recent literature. Many tumors result from the alteration of paracrine growth factors pathways. Growth factors mediate a wide variety of biological processes such as development, tissue repair and tumorigenesis, and also contribute to cellular proliferation and transformation in neoplastic cells. OBJECTIVES: This study evaluated the expression of fibroblast growth factor-2 (FGF-2), transforming growth factor â-1 (TGFâ-1), platelet-derived growth factor-A (PDGF-A) and their respective receptors (FGFR-1, FGFR-2, TGFâR-II and PDGFR-á) in myoepithelial cells from pleomorphic adenomas (PA) by in vivo and in vitro experiments. MATERIAL AND METHODS: Serial sections were obtained from paraffin-embedded PA samples obtained from the school's files. Myoepithelial cells were obtained from explants of PA tumors provided by surgery from different donors. Immunohistochemistry, cell culture and immunofluorescence assays were used to evaluate growth factor expression. RESULTS: The present findings demonstrated that myoepithelial cells from PA were mainly positive to FGF-2 and FGFR-1 by immunohistochemistry and immunofluorescence. PDGF-A and PDGFR-á had moderate expression by immunohistochemistry and presented punctated deposits throughout cytoplasm of myoepithelial cells. FGFR-2, TGFâ-1 and TGFâR-II were negative in all samples. CONCLUSIONS: These data suggested that FGF-2 compared to the other studied growth factors has an important role in PA benign myoepithelial cells, probably contributing to proliferation of ...

Mechanism of the transforming growth factor-â induction of fibronectin expression in hepatic stem-like cells

Transforming growth factor-â1 (TGF-â1) plays an important role in the fibrogenic process in the liver. The aim of the present study was to explore the action of TGF-â1 on fibronectin expression in rat hepatic stem-like cells and the underlying mechanisms. The level of fibronectin expression was determined in hepatic stem-like cells (WB cells) before and after TGF-â1 stimulation by RT-PCR and Western blot methods. Using immunogold transmission electron microscopy and the Western blot method, we observed the result of the expression and the distribution of cAMP, phosphorylated Smad3 and Smad7 before and after TGF-â1 treatment. The levels of fibronectin expression in both mRNA and protein increased 4- to 5-fold after TGF-â1 stimulation, reaching an optimum level after 8 h and then gradually falling back. Similarly, TGF-â1 stimulation resulted in an increase of cAMP in WB cells, peaking at 8 h. After treatment with TGF-â1 for 24 h, the expression of cAMP gradually decreased. In addition, we found that TGF-â1 treatment also contributed to the increased expression and to changes in cellular distribution of phosphorylated Smad3 (translocation from the cytoplasm to the nucleus) and Smad7 (translocation from the nucleus to the cytoplasm) in WB cells. The present study demonstrates that TGF-â is involved in the fibrogenic process in hepatic stem cells through up-regulation of fibronectin expression, and the mechanisms underlying this process may be associated with the activation of cAMP and Smad pathways.

Genetic Analysis of TGFA, MTHFR, and IFR6 in Korean Patients Affected by Nonsyndromic Cleft Lip with or without Cleft Palate (CL/P)

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial birth defect that is the result of a mixture of genetic and environmental factors. While studies have identified a number of different candidate genes and loci for the etiology of CL/P, the results have not been consistent among different ethnic groups. To study the genetic association of the candidate genes in Korean patients affected by CL/P, we genotyped 97 nonsyndromic CL/P patients and 100 control individuals using single nucleotide polymorphic markers at the MTHFR, TGFA, and IRF6 genes. We report that the T3827C marker at TGFA showed significant association with nonsyndromic CL/P, but all the other markers tested were not significantly associated with nonsyndromic CL/P in Korean patients.

The expression of HB-EGF (heparin binding epidermal growth factor) and TGF-A (transforming growth factor alpha) during liver regeneration after partial hepatectomy in mice

The expression of HB-EGF (heparine binding epidermal growth factor) in cells of mice increased just after partial level removal in hapatectomy and reached maximal value 3 hours later. TGF-A expression in mice cells after 2/3 hepatectomy reduced in comparing with control in 3 first hours later and increased in 6 hours later

Influence of Transforming Growth Factor-alpha on Expression of Matrix Metalloproteinase-2, 9 and Epidermal Growth Factor Receptor Gene in the Mouse Blastocysts / 대한불임학회지

No abstract available.

Comparison of the promoting effect on proliferation by secretory-and transmem-brane transforming growth factor-a / 中国免疫学杂志

Abstract Objective:The effects of both TM-TGFa and S-TGFa on proliferation were compared to explore the biological characteristics of the two forms of TGF-a.Methods:The proliferation of mouse fibroblast cell line NIH3T3 and its expression of PCNA were determined by the methods of MTT and histochemical technique. The level of IL-6 mRNA in HaCaT cell line was tested by in situ hybridization. Results:The two forms of TGFa were able to promote cell proliferation,PCNA expression and IL-6 mRNA transcription.The effects of S-TGFa had been shown stronger than that of TM-TGFa( P

THE INHIBITION OF CELL PROLIFERATION IN CARCINOMA OF LARGE INTESTINE BY TRANSFORMING GROWTH FACTOR-ALPHA / 肿瘤研究与临床

Objective To observe the inhibition of transforming growth factor-alpha(TGFa) anti-senseoligodeoxynucleotides on the malignant proliferation of HR8348 cell line. Methods Using the TGFa anti-sense oligodeoxynucleotides, composed of 23 and indifferent oligodeoxynucleotides, to affect the HR8348cell. By observing the cell growth inhibiton, 3H-TdR incorporation,mRNA hybridization and the cell cycleanalysis to identify the inhibiting effects of TGFa anti-sense oligodeoxynucleotides and its mechanism.Results TGFa anti-sense oligodeoxynucleotides can Inhibit the proliferation of HR8348 cell, DNA0synthesis,mRNA expression,and defer the transition period of G,/G, phase to S phase. Conclusion TGFaanti-sense oligodeoxynucleotides can inhibit the malignant proliferation of HR8348 cell effectively.

Distinct Expressions of TGF-a among Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: Transforming growth factor-a(TGF-a) is a polypeptide cytokine related to cell proliferation and transformation. TGF-a binds to EGF receptor and stimulating DNA synthesis in liver cell. The hepatitis B virus (HBV) by itself is also believed to play a role in the hepatic carcinogenesis. Recently, it was reported that TGF-a and HBV were synergistic in action with rapid appearance of hepatocelluar carcinoma in bitransgenic mice. Although TGF- a is thought to play an important role in hepatocarcinogenesis, its expression during the natural history of HBV hepatitis was poorly understood. This investigation was performed to elucidate the dynamic changes and istinct immunohistochemical staining patterns in the course of chronic HBV hepatitis with specific reference to hepatocelluar carcinoma and to explain the role of TGF-a in the pathogenesis of hepatocelluar carcinoma. MATERIALS/METHODS: Employing TGF-a monoclonal antibody, signal detection was carried out by peroxidase-conjugated streptavidin in deparaffinized liver tissue sections taken from HBsAg positive patients. All of the liver tissue sections were proven HBV DNA positive by in situ hybridization. Immunohistochemical staining was performed in the tissue sections obtained from four normal controls, six from patients with chronic persistent hepatitis, five with chronic active hepatitis, eight with liver cirrhosis and eleven with hepatocellular carcinoma. RESULTS: The patterns of TGF-a immunoreactivity were cytoplasmic-grain types in normal controls and chronic persistent hepatitis, honeycomb types in chronic active hepatitis, occasional cytoplasmic-flooding types in liver cirrhosis, and cytoplasmic-grape types in hepatocellular carcinoma. A Shapiro-Wilk W test for frequency table analysis for the expression of TGF-a in these different disease groups was statistically significant. CONCLUSION: These data suggest that step-wise distinct expression of TGF-a enhancement in HBV associated chranic liver diseases which eventually resulted in the development of hepatocellular carcinoma were conceivably due to dysregulation of liver cell cycles by both HBV and TGF-a during the persistent repetition of cell cycles.

Immunohistochemical Investigation on Expression of Hepatitis B Surface Antigen, Transforming Growth Factor-alpha, and Proliferating Cell Nuclear Antigen in Hepatocellular Carcinoma

In an attempt to evaluate the expression of hepatitis B surface antigen(HBs Ag), transforming growth factor-ct(TGF-alpha), and proliferating cell nuclear antigen(PCNA) in hepatocellular carcinoma(HCC), an immunohistochemical investigation(ABC method) was performed using 31 surgically resected HCCS. The authors examined the expression rate and patterns, histopathologic correlation, and inter-relationships among these expressions. The results were summarized as follows. 1) Among 25 seropositive HCCS, 15 cases showed tissue expression of HBs Ag(60.0%), being expressed as a predominantly cytoplasmic pattern. Its expression rate in low grade HCC was significantly high(76.9%), in contrast to a low rate in high grade HCC(41.7%)(P<0.05). Adjacent nonenoplatic tissue showed a higher expression rate(82.6%). 2) TGF-alpha was expressed in 23 of 31 cases of HCC(74.3%). The intensity and extent of its expression did not correlate tyros with histopathologic features. Bile duct epithelium, juxtaposed and/or entrapped liver cells, and cirrhotic nodules were variably expressed, of which intense peripheral reaction within the nodules was frequently noted. 3) PCNA was expressed throughout the neoplastic tissue of HCC. Its index was significantly high(34.4 13.6), being compared to low index index(3.5 2. 1) in the nonneoplastic tissue(P<0.005). High grade tumors revealed a higher index than the low grade tumors(P<0.05). Conclusively, this data confirms that PCNA index offers useful information about cell proliferation associated with histologic degrees of malignancy of HCC, albeit TGF-alpha is also involved in cellular proliferation of both liver cell and bile duct epithelium. Changes in incidence and cellular localization of HBs Ag expression between the neoplastic and nonneoplastic tissues suggest that an integrated viral genome could be functionally altered during hepatocarcinogenesis. A significant inter-relationship among these expressions was not observed.

Expression of Trans forming Growth Factor-a and Proliferating Cell Nuclear Antigen in Human Gliomas

To evaluate the expression of transforming growth factor-alpha(TGF-alpha) and proliferating cell nuclear antigen(PCNA) and its relation to the differentiation of the tumors, immunohistochemical studies were performed in 49 human gliomas. Tumors were graded by a 3-grade-system; grade I=low grade glioma, grade Il=anaplastic glioma, grade III=glioblastoma multiforme. TGF-A and PCNA were predominantly expressed in malignant gliomas compared with benign gliomas. Malignant gliomas revealed 87% TGF-A reactivity, while benign gliomas revealed 26% TGF-A reactivity. The proliferation index with PCNA was 26%+/-7%(mean+/-standard deviation) in malignant gliomas and 5%?% in benign gliomas. A strong positive correlation between tumor grade and extent of TGF-A and PCNA expression was found(P<0.0001, Chi square and P<0.002, T-test). Synchronous expression of TGF-A and PCNA was observed in 16 cases(33%). The results of this study support the suggestion that the expression of TGF-A might be a useful prognostic indicator in human gliomas.

Immunohistochemical obervation of EGF,TGF - alpha and EGF-R in psoriatic epidermis / 대한피부과학회지

Epidermal growth factor(KGF) and transforming growth factor arpha(TGF-a) are polypeptides of 53 amd 50 amino acid residuies. Both bind to epidermal growth factor receptor (EGR-R) leading to phosphorylation of the receptor, enhancement of its tyrosine-specific kinase activity and ultimately to stimulation of cell growth. To study he role of EGF, TGF-a, and EGF-R in differentiation and hyperproliferation of cell, we se lected psoriasis vulgaris, because the affected keratinocyte may house both an abnormally increased proliferative capacity and an abnormally differentiated state. The biopsy specimens were taken from involved and uninvolved skin of 20 patients with psoriasis and immunoperoxidase studies with formalin-fixed paraffin-embedded tissues were performed with EGF, TGF-a and EGF-R useing the Vectastain ABC irnmunoperoxidase stain system. The antibodies were used at a concentration of 6 ug/ml In involved psoriatic skin, distributions of TGF-a and EGF-R were increased in all layers of epidermis as compared to normal, uninvolved psoriatic skin, in which chev were showed to the basal and parabasal layers. However, distribution of EGF was weekly positive in the basal layers of epidermis in both involved and uninvolved skin with no difference between toem. These results suggest that increased distribution of TGF-a and EGF-R may be involved in hypoproliferative state of epidermal keratinocytes in psoriatic lesion.