No abstract available.
Transforming Growth Factor alpha* ; Transforming Growth Factors*

To investigate whether transforming growth factor alpha (TGF alpha) treatment of human ovarian cancer cells was associated with the induction of c-myc protooncogene, the expression of this gene in NIH:OVCAR-3 cells was examined. TGF alpha induced increase in c-myc mRNA level, with a peak after 1 h of treatment; this stimulation was dose-dependent, with an optimal concentration of 5 ng/ml TGF alpha. Its primary action is probably at the transcription level since the half-life of c-myc mRNA measured in the presence of actinomycin D was not modified by TGF alpha treatment. In addition, TGF alpha stimulation of c-myc mRNA did not require protein synthesis since it was not suppressed by cycloheximide treatment. Antisense phosphorothioate oligonucleotide to c-myc specifically inhibited the TGF alpha-stimulated c-Myc protein expression and growth of NIH:OVCAR-3 cells. Our results indicate that induction of c-myc expression by TGF alpha plays an important role in the growth of NIH:OVCAR-3 cells.
Cycloheximide ; Dactinomycin ; Half-Life ; Humans* ; Ovarian Neoplasms* ; RNA, Messenger ; Transforming Growth Factor alpha ; Transforming Growth Factors*

BACKGROUND: Transforming growth factor-(TGF-alpha) is a acidic, heat-stable, 50 amino acid polypeptide which is related to cellular proliferation, malignant transformation, and angiogenesis. There are many similarities between keratoacanthoma(KA) and squamous cell carcinoma(SCC). So, it is often difficult to differentiate keratoacanthoma and squamous cell carcinoma, clinically and histologically. OBJECTIVE: Our purpose was to examine the patterns of TGF-alpha expression on KA and SCC using immunohistochemical staining and to evaluate the usefulness of the immunohistochemical staining with antihuman TGF-alpha antibody on differentiation between KA and SCC. METHODS: Formalin-fixed, paraffin-embedded specimens that had confirmed to KA(n=12) or SCC(n=10) were performed by immunoperoxidase staining with monoclonal antihuman TGF-alpha antibody RESULTS: All of KA dmonstrated a diffuse pattern within tumor lobules, but, at the peripheral rim of cells, showed unstained pattern. In contrast to KA, 40% of the SCC had patchy infiltration within tumor lobules, and 60% of the SCC had diffuse pattern which was similar to the pattern found in KA. All of SCC showed well-defined staining at peripheral cells. CONCLUSION: Immunohistochemical staining with antihuman TGF-alpha antibody could be used on differentiation between KA and SCC.
Carcinoma, Squamous Cell* ; Cell Proliferation ; Keratoacanthoma* ; Transforming Growth Factor alpha ; Transforming Growth Factors*

BACKGROUND: Transforming growth factor-(TGF-alpha) is a acidic, heat-stable, 50 amino acid polypeptide which is related to cellular proliferation, malignant transformation, and angiogenesis. There are many similarities between keratoacanthoma(KA) and squamous cell carcinoma(SCC). So, it is often difficult to differentiate keratoacanthoma and squamous cell carcinoma, clinically and histologically. OBJECTIVE: Our purpose was to examine the patterns of TGF-alpha expression on KA and SCC using immunohistochemical staining and to evaluate the usefulness of the immunohistochemical staining with antihuman TGF-alpha antibody on differentiation between KA and SCC. METHODS: Formalin-fixed, paraffin-embedded specimens that had confirmed to KA(n=12) or SCC(n=10) were performed by immunoperoxidase staining with monoclonal antihuman TGF-alpha antibody RESULTS: All of KA dmonstrated a diffuse pattern within tumor lobules, but, at the peripheral rim of cells, showed unstained pattern. In contrast to KA, 40% of the SCC had patchy infiltration within tumor lobules, and 60% of the SCC had diffuse pattern which was similar to the pattern found in KA. All of SCC showed well-defined staining at peripheral cells. CONCLUSION: Immunohistochemical staining with antihuman TGF-alpha antibody could be used on differentiation between KA and SCC.
Carcinoma, Squamous Cell* ; Cell Proliferation ; Keratoacanthoma* ; Transforming Growth Factor alpha ; Transforming Growth Factors*

PURPOSE: This study was designed to identify the possible mechanism of insensitivity of DU145 prostate cancer cells to the transforming growth factor (TGF)-beta1-mediated growth inhibition. MATERIALS AND METHODS: DU145 cells were treated with 4, 40, 100 pM TGF-beta1 for 3, 6, 9 days. Initially we performed the growth assay. After that, we analysed the change of cell cycle using fluorescence flow cytometry. At each time point, Western blot analysis with cell pellets was performed to investigate the change of expressions of epidermal growth factor(EGF), TGF-alpha, EGF receptor(EGFR) and TGF receptorII(TbetaR-II) proteins. RESULTS: The growth rate of TGF-beta1-treated cells was initially suppressed, but over time returned to control level. Flow cytometric analysis revealed that TGF-beta1-treated cells showed an increase in apoptotic/G1 phases, and concurrent decrease in S, G2/M phases until 6days. On day 9, however, TGF-beta1-treated cells showed a persistent increase of apoptotic unclei in spite of recovery of apoptotic/G1, S and G2/M phases. Western blot analysis showed that the intensity of EGF or TGF-alpha band decreased in dose-sependent manner on day 6. However, the intensity of each band increased up to the control level on day 9. the expression of EGFR or TbetaR-II protein did not change after treatment of TGF-beta1. CONCLUSIONS: these results suggest that EGF and TGF-alpha sould mediate in part the escape fron the inhibitory effect of TGF-beta1 in DU145 cells.
Blotting, Western ; Cell Cycle ; Epidermal Growth Factor* ; Flow Cytometry ; Fluorescence ; Prostate* ; Prostatic Neoplasms* ; Transforming Growth Factor alpha ; Transforming Growth Factor beta1 ; Transforming Growth Factors ; United Nations

PURPOSE: We evaluated the effects of epidermal growth factor(EGF) and transforming growth factor-alpha (TGF-alpha) on the growth of human transitional cell carcinoma cell lines. MATERIALS AND METHODS: T-24, KK47 and KU-1 cell lines established from human transitional cell carcinoma tissues were used. We cultured the cell lines in serum-free media for 48 hours and then administered EGF and TGF-alpha in the concentrations of 0.1ng/ml, 1ng/ml, 10ng/ml and 100ng/m1 respectively. We analysed the effects by MTT assay at 144 hours. RESULTS: There were statistically significant stimulatory effects on the growth of three cell lines in all cultures. Enhanced growth was also observed in the culture with administration of EGF and TGF-alpha simultaneously. None of stimulatory effects were dose-related. CONCLUSIONS: We should take into consideration of possible role of EGF which are excreted in urine in very high concentration in a biologically active form and TGF-alpha of which urinary level increases with various type of bladder injuries in occurrence, progression and recurrence of transitional cell carcinoma of urothelium.
Carcinoma, Transitional Cell* ; Cell Line* ; Culture Media, Serum-Free ; Epidermal Growth Factor* ; Humans* ; Recurrence ; Transforming Growth Factor alpha ; Transforming Growth Factors ; Urinary Bladder ; Urothelium

Meningioma is the most common primary intracranial neoplasm that originates from the meningothelial cells. It occurs mainly in adults, and has a female preponderance. It is classically classified into three main types: meningotheliomatous or syncytial type, fibrous or fibroblastic type, and transitional type. Transforming growth factor alpha(TGF-alpha) was known as a neoplastic transformer found in the neoplastic tissue of the brain rather than in normal tissue in the neoplastic tissue, the expression of the TGF-alpha was more intense in the malignant rather than benign tumor, but the expression of the TGF-alpha on the meningioma was not reported. Transforming growth factor-beta (TGF-beta) was known as a peptide which is involved in the proliferation of the mesenchymal cells and the other many physiologic processes. Tumor necrosis factor(TNF) has a selective necrotic action of the neoplastic cells without influence on normal tissues. Epidermal growth factor (EGF) and epidermal growth factor receptor(EGR) have a control effect on cellular proliferation and differentiation and the expression of the EGR in breast cancer has a reverse correlation to the expression of the estrogen receptor(ER). The meningioma is the most common host tumor of breast cancer among the intracranial neoplasm, so, presence of some estrogen receptors in the meningioma is suspected. The correlation of the estrogen receptor expression to EGR expression in the meningioma is the concern of this study. Therefore, the authors have observed the meningioma on the basis of the expression of the ER, TGF-alpha, TGF-beta, TNF-beta, EGF and EGR according to the immunohistochemical stain and polymerase chain reaction(PCR), and the results obtained were as follows. The expressions of the TGF-alpha, TGF-beta were weakly positive in 4 out of 25 examined cases, and the expressions of the EGF and EGR, were more intensely positive in 2 out of 25 examined cases, especially in the vascular wall and perivascular area. TNF-beta expression was weakly positive to focal area only in one case of the meningotheliomatous type. The ER expression was weakly positive to focal areas. The subtypes of meningioma expressing positivity were meningotheliomatous and transitional type, which wer not related to tumor aggressiveness or poor prognosis. In conclusion, ER,EGF-alpha, TGF-beta, TNF-beta, EGF and EGR were experssed in the meningionma, and it is suspected that these factors may be involved in the tumorigenesis or "host" tumor action rather than in tumor aggressiveness.
Adult ; Brain ; Brain Neoplasms ; Breast Neoplasms ; Carcinogenesis ; Cell Proliferation ; Epidermal Growth Factor ; Estrogens ; Female ; Fibroblasts ; Humans ; Lymphotoxin-alpha ; Meningioma* ; Necrosis ; Polymerase Chain Reaction* ; Prognosis ; Receptors, Estrogen ; Transforming Growth Factor alpha ; Transforming Growth Factor beta ; Transforming Growth Factors

PURPOSE: Tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 have been shown to play important roles in allograft rejection of various organs. This study was performed to evaluate the association of TNF-alpha and TGF-beta1 genes and renal allograft dysfunction. METHODS: Five TNF-alpha ( 1,031 T/C, 863 C/A, 857 C/T, 308 G/A, 238 G/A) and two TGF-beta1 (codon 10 T/C, codon 25 G/C) single nucleotide polymorphism (SNP) sites were studied using PCR-SSCP and PCR-RFLP methods in 100 controls and 165 patients underwent renal transplantation. For the TGF-beta1 gene, we also studied the polymorphism of donors. RESULTS: The allele frequencies of each SNP sites in controls were not different from those of patients. The phenotype frequency of TNF-alpha high producer type, 308 A was significantly higher in the patients with recurrent acute rejection episodes (REs) compared with patients with no or one RE (38.5% vs. 9.2%, P=0.007). The frequency of TGF-beta1 low producer genotype, codon 10 CC was also significantly higher in the patients with recurrent REs (53.8% vs. 22.4%, P=0.029). Analysis of chronic renal allograft dysfunction (CRAD) revealed that the TGF-beta1 high producer type, codon 10 T allele in donors was associated with CRAD (66.7% vs. 48.2%, P=0.043). This association was significant only among patients with recurrent REs. Occurrence of CRAD was not influenced by TGF-beta1 polymorphisms in the patients. CONCLUSION: These results would be useful for predicting high risk group for acute rejection or CRAD in renal transplantation and might be useful for implying individualized immunosuppressive therapy.
Alleles ; Allografts* ; Codon ; Gene Frequency ; Genotype ; Humans ; Kidney Transplantation ; Phenotype ; Polymorphism, Single Nucleotide ; Tissue Donors ; Transforming Growth Factor beta1* ; Transforming Growth Factors ; Tumor Necrosis Factor-alpha*

Based upon the concept that carcinogenesis is associated with apoptosis, specific therapies designed to enhance the susceptibility of cancer cells to undergo apoptosis could be developed. Thus, in this paper, it was designed to investigate whether, using rat animal model with chemical-induced hepatocellular carcinoma, TGF-1 in vivo could induce apoptosis in cancer. The chemical hepatocarcinogenic procedure of Solt-Farber method was used on Sprague-Dawley rats. Experimental groups were divided into group A treated with the standard Solt-Farber regimen of diethylnitrosamine (DEN) and 2-Acetaminofluorene (AAF), group B TGF-, group C TGF-1, and group D adriamycin after hepatocellular carcinoma developed. For detection of apoptotic cells, apoptotic indices were examined by the in situ end DNA labelling method. The expression of proliferating cell nuclear antigen was examined by immunohistochemical staining. Apoptosis of rat hepatocellular carcinoma cells increased significantly to 4.92+/-2.32/HPF in the group C compared with the control group (A) (2.54+/-1.13/HPF; P<0.05). Two distinctly different populations of proliferating hepatocellular carcinoma cells were identified. The cells at G1/S boundary (weak granular staining) increased to 15.75+/-6.19/HPF and 6.45+/-2.93/HPF in the groups C and D, respectively, but decreased to 2.42+/-2.06/HPF in the group B compared with the control group (A) (6.38+/-2.18/HPF; p<0.05). The cells at S phase (strong granular staining) increased to 3.37+/-2.69/HPF in the group B but decreased to 0.32+/-0.47/HPF in the group D (p<0.05). In conclusion, these results indicate that the TGF-1 may be used as an effective anticancer agent.
Animals ; Apoptosis ; Carcinogenesis ; Carcinoma, Hepatocellular* ; Diethylnitrosamine ; DNA ; Doxorubicin ; Models, Animal ; Proliferating Cell Nuclear Antigen ; Rats* ; Rats, Sprague-Dawley ; S Phase ; Transforming Growth Factor alpha ; Transforming Growth Factor beta1* ; Transforming Growth Factors*

transforming growth factor related with oral cancer. The purpose of this paper was to find the expression patterns of transforming growth factor alpha and beta during the stages of complete oral carcinogenesis model in hamster. 0.5% 9, 10-dimethyl-1, 2-benzanthracene(DMBA) in mineral oil was topically applied to the buccal pouch of 75 hamster three times a week during the experimental periods. The experimental animals were subdivided into two groups of control and experiment. Only the mineral oil was applied to the control group. 0.5% DMBA in mineral oil was applied to the experimental groups of 6, 8, 10, 12, 14, 16, 18 and 20 weeks. The expression of the TGF-alpha and TGF-beta protein were evaluated by the distribution and intensity of positive cells during the carcinogenesis using the immunohistochemical study. The following results were obtained ; 1. The buccal pouch epithelium of hamster was histologically changed to the dysplasia at 6, 8, 10 weeks, carcinoma in situ at 12 weeks, and squamous cell carcinoma at 14 weeks. 2. The expression of the TGF-alpha was restricted to the parabasal and basal layers of the normal and dysplastic mucosa, but those positive cells were extended to the spinous layers of the epithelium in the carcinoma. 3. The degree of TGF-alpha expression was markedly decreased in the carcinoma at 16, 18, 20. The strong positive staining in the center of cancer islands and weak positive staining in periphery of tumor were seen at the stage of squamous cell carcinoma. 4. The positive index of the TGF-alpha had a tendency to increase with DMBA- applied time. There was a statistically significant difference between 12, 18, 20 experimental group and control group(p<0.05). 5. The expression of TGF-beta was shown at the cytoplasm of all control and experimental groups, and the parabasal and basal layers of the normal and dyslastic mucosa, but it was shown at the basal layers of the epithelium in the carcinoma. 6. TGF-beta was expressed diffusely at 16, 18, 20 experimental gruop. The strong positive staining in the center of cancer islands and positive staining in periphery of tumor were seen at the stage of squamous cell carcinoma. Form the above finding, the expression of TGF-alpha and TGF-beta in oral carcinogenesis model seems to have two formal stages, the first being an overexpression step as reaction to uncontrolled growth and the second being one in which exteral protein accumulate in the surrounding stroma and intracytoplasm. Overexpression of TGF-alpha and TGF-beta may have important cooperative roles for the promotion of cancer and factor of prognosis.]]>
9,10-Dimethyl-1,2-benzanthracene ; Animals ; Carcinogenesis ; Carcinoma in Situ ; Carcinoma, Squamous Cell ; Cricetinae ; Cytoplasm ; Epigenomics ; Epithelium ; Islands ; Mineral Oil ; Mouth Neoplasms ; Mucous Membrane ; Prognosis ; Transforming Growth Factor alpha ; Transforming Growth Factor beta ; Transforming Growth Factors